leptin and Cat-Diseases

Obesity is one of the most prevalent health conditions in humans and companion animals globally. It is associated with premature mortality, metabolic dysfunction, and multiple health conditions across species. Obesity is, therefore, of importance in the fields of medicine and veterinary medicine. The regulation of adiposity is a homeostatic process vulnerable to disruption by a multitude of genetic and environmental factors. It is well established that the heritability of obesity is high in humans and laboratory animals, with ample evidence that the same is true in companion animals. In this review, we provide an overview of how genes link to obesity in humans, drawing on a wealth of information from laboratory animal models, and summarise the mechanisms by which obesity causes related disease. Throughout, we focus on how large-scale human studies and niche investigations of rare mutations in severely affected patients have improved our understanding of obesity biology and can inform our ability to interpret results of animal studies. For dogs, cats, and horses, we compare the similarities in obesity pathophysiology to humans and review the genetic studies that have been previously reported in those species. Finally, we discuss how veterinary genetics may learn from humans about studying precise, nuanced phenotypes and implementing large-scale studies, but also how veterinary studies may be able to look past clinical findings to mechanistic ones and demonstrate translational benefits to human research.

Topics: Animals; Cat Diseases; Cats; Comorbidity; Dog Diseases; Dogs; Genetic Predisposition to Disease; Genome-Wide Association Study; Horse Diseases; Horses; Humans; Leptin; Melanocortins; Metabolic Diseases; Obesity; Pets

Feline obesity is a common and preventable disease, posing a myriad of health risks and detriments. Specially formulated diets and restricted feeding may serve as an intervention strategy to promote weight loss and improve feline health. In this study, our objective was to determine the effects of restricted feeding and weight loss on body composition, voluntary physical activity, blood hormones and metabolites, and fecal microbiota of overweight cats. Twenty-two overweight adult spayed female and neutered male cats [body weight (BW) = 5.70 ± 1.0 kg; body condition score (BCS) = 7.68 ± 0.6; age = 4 ± 0.4 yr] were used in a weight loss study. A control diet (OR) was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline (week 0), cats were allotted to OR or a test diet (FT) and fed to lose ~1.0% BW/wk for 24 wk. At baseline and 6, 12, 18, and 24 wk after weight loss, dual-energy x-ray absorptiometry scans were performed and blood samples were collected. Voluntary physical activity was measured at weeks 0, 8, 16, and 24. Fecal samples were collected at weeks 0, 4, 8, 12, 16, 20, and 24. Change from baseline data were analyzed statistically using the Mixed Models procedure of SAS, with P < 0.05 considered significant. Restricted feeding of both diets led to weight and fat mass loss, lower BCS, and lower blood triglyceride and leptin concentrations. Cats fed the FT diet had a greater reduction in blood triglycerides and cholesterol than cats fed the OR diet. Restricted feeding and weight loss reduced fecal short-chain fatty acid, branched-chain fatty acid, phenol, and indole concentrations. Fecal valerate concentrations were affected by diet, with cats fed the OR diet having a greater reduction than those fed the FT diet. Fecal bacterial alpha diversity was not affected, but fecal bacterial beta diversity analysis showed clustering by diet. Restricted feeding and weight loss affected relative abundances of 7 fecal bacterial genera, while dietary intervention affected change from baseline relative abundances of 2 fecal bacterial phyla and 20 fecal bacterial genera. Our data demonstrate that restricted feeding promoted controlled and safe weight and fat loss, reduced blood lipids and leptin concentrations, and shifted fecal metabolites and microbiota. Some changes were also impacted by diet, highlighting the importance of ingredient and nutrient composition in weight loss diets.. The objective of this study was to determine the effects of diet, restricted feeding and weight loss on body composition, voluntary physical activity, blood hormones and metabolites, and fecal metabolites and microbiota of overweight cats. Overweight cats were allotted to a control diet (OR) or weight loss diet (FT) and fed to lose ~1.0% body weight/week for 24 wk. Body weight, body composition, and voluntary physical activity were measured, while fecal and blood samples were collected over time. Restricted feeding led to weight and fat mass loss, and lower blood triglyceride and leptin concentrations. Cats fed FT had a greater reduction in blood triglycerides and cholesterol than cats fed OR. Restricted feeding reduced fecal metabolite concentrations and affected relative abundances of 7 fecal bacterial genera. Fecal bacterial beta diversity analysis showed clustering by diet. Dietary intervention affected change from baseline relative abundances of 2 fecal bacterial phyla and 20 fecal bacterial genera. Our data demonstrate that restricted feeding promoted controlled and safe weight and fat loss, reduced blood lipids and leptin concentrations, and shifted fecal metabolites and microbiota. Some dietary differences were noted, highlighting the importance of ingredient and nutrient composition in weight loss diets.

Topics: Animal Feed; Animals; Bacteria; Body Composition; Body Weight; Cat Diseases; Cats; Diet; Feces; Female; Leptin; Male; Microbiota; Overweight; Weight Loss

Obesity leads to insulin resistance and is a major risk factor for the development of diabetes mellitus in cats. Prevention of obesity and obesity-induced insulin resistance is difficult, and reliable long-term strategies are currently lacking. Retinoid-related orphan receptor gamma (RORγ) was recently identified as an important transcription factor in the development of large insulin-resistant adipocytes in mice and humans. RORγ negatively affects adipocyte differentiation through expression of its target gene matrix metalloproteinase 3 (MMP3) and promotes the development of large insulin-resistant adipocytes. Preliminary studies in mice showed that RORγ can be inhibited by its ligand tetra-hydroxylated bile acid (THBA). In the present study, serum THBA levels were determined in healthy and diabetic cats. Moreover, potential side effects and the effects of THBA supplementation on adipocyte size, mRNA expression of RORγ, MMP3, interleukin 6, tumor necrosis factor α, adiponectin and leptin in feline subcutaneous adipocytes and insulin sensitivity were investigated in healthy normal weight cats. Thirteen healthy and 13 diabetic cats were used for determination of serum THBA level, and six healthy normal-weight cats were included in a feeding trial. Similar THBA levels were determined in serum of healthy and diabetic cats. Supplementation of 5 mg/kg THBA for 8 wk did not cause any negative effect on feeding behavior, general condition and blood parameters of tested cats. It significantly reduced adipocyte size and mRNA expression of MMP3, interleukin 6, and tumor necrosis factor α in adipocytes, while mRNA expression of adiponectin significantly increased and mRNA expression of RORγ and leptin remained unchanged. Administration of THBA did not influence fasting blood glucose levels or the response of cats to acute insulin administration. Based on these results, THBA is palatable and is considered safe for use in cats. It reduces expression of MMP3 and promotes the development of small adipocytes with increased expression of adiponectin and reduced expression of interleukin 6 and tumor necrosis factor α. Further studies are recommended to evaluate the effect of THBA on adipocyte size and insulin sensitivity in obese cats.

Topics: Adipocytes; Adiponectin; Animals; Bile Acids and Salts; Cat Diseases; Cats; Diabetes Mellitus; Insulin; Insulin Resistance; Interleukin-6; Leptin; Matrix Metalloproteinase 3; Mice; Obesity; RNA, Messenger; Rodent Diseases; Tumor Necrosis Factor-alpha

We monitored changes in serum leptin, adiponectin, and resistin concentrations in obese cats during weight loss. Six naturally developed obese cats were fed low-fat, high-fiber dry food during a 9-week experimental period. Serum leptin, adiponectin, and resistin concentrations were measured at week 0, 4, 8, and 9. Body weight became significantly lower week 4 onward than that at week 0 (P<0.05 or 0.01). At week 9, serum leptin concentrations were significantly lower than those at week 0 (P<0.05). Contrarily, serum adiponectin and resistin concentrations did not significantly differ within the 9 weeks. While serum leptin levels were strongly positively correlated with body weight (r=0.923, P<0.001), serum adiponectin levels were moderately negatively correlated with it (r=-0.529, P<0.01), with serum resistin having a no correlation with body weight. Serum leptin levels might be more closely related with pathogenesis of adiposity than serum adiponectin or resistin in cats.

Topics: Adiponectin; Animals; Cat Diseases; Cats; Diet; Female; Leptin; Obesity; Resistin; Weight Loss

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise in BHB and NEFA. Glucose clearance was unaltered, although less insulin was secreted during the IVGTT (p = .056) suggesting improved insulin sensitivity. IVITT was unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post-D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia.

Topics: 3-Hydroxybutyric Acid; Adiponectin; Animals; Cat Diseases; Cats; Diabetes Mellitus; Drinking; Electrolytes; Fatty Acids, Nonesterified; Female; Fructosamine; Glucagon; Glucose Tolerance Test; Glycosuria; Hypoglycemic Agents; Leptin; Male; Nitriles; Obesity; Sodium-Glucose Transporter 2 Inhibitors

Overweight and obesity are multifactorial diseases caused by an imbalance in energy metabolism. An underlying genetic predisposition is often a factor in these conditions. In the cat breeding family of the Institute of Animal Nutrition at the Vetsuisse Faculty, University of Zurich, a segregating overweight phenotype with a genetic contribution was observed. From this breeding family, 26 kittens were followed from birth up to 8 months of age. During this time, food intake was measured using an automatic feeding station, and energy expenditure was investigated using indirect calorimetry at the ages of 4 and 6 months. Dual-energy X-ray absorptiometry (DEXA) was performed and blood glucose, leptin and insulin were measured at the ages of 4, 6 and 8 months. The kittens were also weighed daily for the first 2 weeks of life, every second day until weaning and once per week until 8 months of age. The body condition score (BCS) was evaluated monthly between 2 and 8 months of age. The main finding of this study is that a predisposition to overweight is connected to a higher food intake early in life, with no significant alterations in energy expenditure. The leptin blood levels were related to body fat percentage, and insulin sensitivity did not seem to be affected.

Topics: Animals; Body Composition; Calorimetry, Indirect; Cat Diseases; Cats; Eating; Energy Intake; Energy Metabolism; Female; Leptin; Obesity

Leptin and ghrelin, two peptide hormones with antagonistic effects on satiety and energy balance, could be involved in the pathogenesis of weight loss and polyphagia in cats with hyperthyroidism. Leptin generally decreases appetite and increases energy expenditure, while ghrelin exerts the opposite effects.. Leptin and ghrelin were measured in 42 client owned hyperthyroid cats with a body condition score (BCS) ≤ 5/9 before (T0) and 4 weeks after radioactive iodine treatment (RAIT) (T1). Dependent on the serum total thyroxine concentration concentration at T1, cats were sub-classified as still hyperthyroid (ht-ht) (n = 4), euthyroid (ht-eu) (n = 10) or hypothyroid (ht-hypo) (n = 28). Results were compared to those of 22 healthy, euthyroid control cats with a comparable BCS (≤ 5/9) and age (≥ 8 years) to hyperthyroid cats.. At T0, there were no significant differences between hyperthyroid and control cats for leptin (p = 0.06) or ghrelin concentrations (p = 0.27). At T1, leptin significantly decreased in ht-hypo cats compared to T0 (p = 0.0008) despite a significantly increased body weight in this group (p = 0.0001). Serum ghrelin concentrations did not differ between hyperthyroid cats with a history of polyphagia compared to non-polyphagic cats (p = 0.42). After RAIT, ghrelin concentration significantly increased in all hyperthyroid cats (p < 0.0001), as well as in the subgroups ht-eu (p = 0.014) and ht-hypo (p < 0.0001) compared to their respective T0 baseline concentrations.. Leptin and ghrelin fluctuations may be indicative of changes in metabolic functions in cats with thyroid dysfunction. Leptin fluctuations occurred independently of body weight in different states of thyroid dysfunction; increasing ghrelin concentrations after RAIT suggest a ghrelin-independent mechanism for polyphagia in hyperthyroid cats.

Topics: Animals; Cat Diseases; Cats; Ghrelin; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Leptin

Leptin is an adipokine, which is in humans with cardiac disease suspected to be involved in myocardial remodeling and thrombus formation. In cats, however, it is not known whether leptin plays a role in cardiac disease, i.e. hypertrophic cardiomyopathy (HCM) and the presence of an atrial thrombus (AT). The objective of the study was therefore to establish whether leptin is transcribed in the feline myocardium and to compare myocardial leptin mRNA concentrations in cats with HCM with and without AT, and in cats without cardiac diseases. Myocardial samples from 15 cats with HCM (five of these with AT), and 12 cats without cardiac diseases were investigated for leptin mRNA expression using quantitative reverse transcriptase PCR, and the transcription levels were correlated with those obtained for a range of cytokines and remodeling parameters. Leptin mRNA expression was detected in the myocardium in all heart regions, with generally higher concentrations in the atria than in the ventricles. Cats with HCM exhibited higher atria and ventricular leptin transcription than cats without cardiac diseases, but reduced ventricular transcription levels in the presence of AT. A positive correlation between leptin, cytokine and remodeling marker transcription levels was observed. The present study shows that leptin is constitutively transcribed in the feline myocardium. The observed increase in leptin mRNA concentrations in the myocardium from cats with HCM and the reduction when an AT is present suggests varying gene activation in different stages of the disease and a potential involvement of leptin in the feline cardiac remodeling process.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Cytokines; Gene Expression Regulation; Heart Atria; Leptin; Male; Myocardium; RNA, Messenger; Thrombosis

Resistin, one of the adipokines that has a cycteine-rich C-terminus, is considered to relate to the development of insulin resistance in rats. However, in cats, there is little knowledge regarding resistin. In this study, we cloned the feline resistin cDNA from adipose tissue by RT-PCR. The feline resistin clone contained an entire open reading frame encoding 107 amino acids that had 72.8%, 75.4%, 50.9% and 51.8% homology with bovine, human, mouse and rat homologues, respectively. In both subcutaneous and visceral adipose tissues, the transcription levels of feline resistin mRNA were significantly higher in obese cats than normal cats, and those of feline adiponectin mRNA were significantly lower in obese cats than normal cats. However, there was no difference in the expression of feline leptin between normal and obese cats. On the other hand, in both normal and obese cats, there were no significant differences in resistin, leptin and adiponectin mRNA levels between subcutaneous and visceral adipose tissues. In cats, the altered expression of resistin and adiponectin mRNA with obesity may contribute to the pathogenesis of insulin resistance and subsequent diabetes mellitus. In addition to feline adiponectin, the feline resistin cDNA clone obtained in this study will be useful for further investigation of the pathogenesis of obesity in cats.

Topics: Adiponectin; Adipose Tissue; Animals; Cat Diseases; Cats; Cattle; Cloning, Molecular; Female; Humans; Leptin; Male; Mice; Obesity; Rats; Resistin; Sequence Homology, Nucleic Acid

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Hyperthyroidism; Leptin; Male; Methimazole; Thyroid Hormones; Thyroxine; Treatment Outcome

To determine associations between serum concentrations of omega-3 polyunsaturated fatty acids and concentrations of adiponectin, leptin, and insulin in healthy cats.. 56 healthy adult client-owned cats.. Body condition score (BCS) was determined, and blood samples were collected after food was withheld for 12 hours. Serum was harvested for fatty acid analysis and measurement of serum concentrations of adiponectin, leptin, insulin, glucose, triglyceride, and cholesterol.. 1 cat was removed because of hyperglycemia. Significant interaction effects between BCS and serum concentrations of eicosapentaenoic acid (EPA) were detected for the analyses of associations between EPA and serum concentrations of adiponectin, insulin, and triglyceride. Cats were categorized into nonobese (BCS, 4 to 6 [n = 34 cats]) and obese (BCS, 7 to 8 [21]) groups; serum concentrations of EPA were directly associated with concentrations of adiponectin and inversely associated with concentrations of insulin and triglyceride in obese cats and were directly associated with concentrations of leptin and inversely associated with concentrations of adiponectin in nonobese cats. Additionally, serum concentrations of docosahexaenoic acid were directly associated with concentrations of adiponectin in obese cats. No significant associations between serum concentrations of docosahexaenoic acid or α-linolenic acid were detected in the analyses for all cats. Female cats had higher serum concentrations of adiponectin and lower concentrations of glucose than did male cats. Increased age was associated with a small increase in serum concentrations of leptin.. EPA may ameliorate the decrease in adiponectin and the increase in insulin and triglyceride concentrations in obese cats.

Topics: Adiponectin; alpha-Linolenic Acid; Animals; Blood Glucose; Body Composition; Cat Diseases; Cats; Cholesterol; Cross-Sectional Studies; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Omega-3; Female; Insulin; Leptin; Male; Obesity; Sex Characteristics; Triglycerides

The propensity of diets of different composition to promote obesity is a current topic in feline medicine. The effects of three meals with different protein:fat ratios on hormones (insulin, acylated ghrelin and amylin) involved in the control of food intake and glucose metabolism were compared. Five lean (two females and three males, 28.6 (sd 3.4) % body fat mass (BFM), mean body weight (BW) 4590 g) and five obese (two females and three males, 37.1 (sd 4.1) % BFM, mean BW 4670 g) adult cats were studied. Only BFM differed significantly between obese and lean cats. The cats were fed a high-protein (HP), a high-fat and a high-carbohydrate diet in a randomised cross-over design. Food intake did not differ between cats fed on the different diets, but obese cats consumed significantly more energy, expressed as per kg fat-free mass, than lean cats. After a 6-week adaptation period, a test meal was given and blood samples were collected before and 0, 30, 60 and 100 min after the meal. Baseline concentrations of glucose, amylin and acylated ghrelin were higher in obese cats than in lean cats, and obese cats showed the highest postprandial responses of glucose and amylin. The HP diet led to higher postprandial amylin concentrations than the other diets, indicating a possible effect of amino acids on beta-cell secretion. Postprandial ghrelin concentrations were unaffected by diet composition. The relationship between insulin, amylin and ghrelin secretion and their relevant roles in food intake and glucose metabolism in cats require further study.

Topics: Acylation; Amyloid; Animals; Blood Glucose; Body Weight; Cat Diseases; Cats; Diet; Dietary Carbohydrates; Dietary Fats; Energy Intake; Female; Food; Ghrelin; Insulin; Insulin-Like Growth Factor I; Islet Amyloid Polypeptide; Leptin; Male; Obesity

Glucocorticoid (GC) action depends on GC plasma concentration, cellular GC receptor expression, and the pre-receptor hormone metabolism catalyzed by 11β-hydroxysteroid dehydrogenase (11β-HSD). 11β-Hydroxysteroid dehydrogenase exists in 2 isoforms; 11β-HSD1 converts inactive cortisone to cortisol, and 11β-HSD2 converts cortisol to cortisone. Increasing evidence in humans and experimental animals suggests that altered tissue cortisol metabolism may predispose to diabetes mellitus (DM). Once DM is established, hyperglycemia and hyperlipidemia may further maintain the abnormal metabolism of cortisol. To gain further insight in this regard, healthy cats were infused for 10 d with lipids (n = 6) or saline (n = 5). At the end of the infusion period, tissue samples from adipose tissue (visceral, subcutaneous), liver, and muscle were collected to determine mRNA expression of 11β-HSD1, 11β-HSD2, and GC receptor by real-time reverse-transcriptase polymerase chain reaction; blood samples were collected to determine plasma cortisol and leptin concentrations. Lipid infusion resulted in greater 11β-HSD1 expression and lower GC receptor expression in visceral and subcutaneous adipose tissue, and lower 11β-HSD2 expression in visceral adipose tissue and liver. Plasma cortisol did not differ. Leptin and body weight increased in lipid-infused cats. In spite of comparable circulating cortisol levels, up-regulation of 11β-HSD1 and down-regulation of 11β-HSD2 expression may result in increased tissue cortisol concentrations in fat depots of hyperlipidemic cats. Down-regulation of GC receptor may represent a self-protective mechanism against increased tissue cortisol levels. In conclusion, hyperlipidemia has a profound effect on 11β-HSD expression and supports the connection between high lipid concentrations and tissue cortisol metabolism.

Topics: 11-beta-Hydroxysteroid Dehydrogenases; Adipose Tissue; Animals; Cat Diseases; Cats; Fatty Acids, Nonesterified; Gene Expression; Glucocorticoids; Glucose Tolerance Test; Hydrocortisone; Hyperlipidemias; Insulin; Leptin; Lipids; Liver; Male; Muscles; Receptors, Glucocorticoid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

The effects of 2 diets with different protein contents on weight loss and subsequent maintenance was assessed in obese cats. The control group [Co; n = 8; body condition score (BCS) = 8.6 +/- 0.2] received a diet containing 21.4 g crude protein (CP)/MJ of metabolizable energy and the high-protein group (HP; n = 7; BCS = 8.6 +/- 0.2) received a diet containing 28.4 g CP/MJ until the cats achieved a 20% controlled weight loss (0.92 +/- 0.2%/wk). After the weight loss, the cats were all fed a diet containing 28.0 g CP/MJ at an amount sufficient to maintain a constant body weight (MAIN) for 120 d. During weight loss, there was a reduction of lean mass in Co (P < 0.01) but not in HP cats and a reduction in leptinemia in both groups (P < 0.01). Energy intake per kilogram of metabolic weight (kg(-0.40)) to maintain the same rate of weight loss was lower (P < 0.04) in the Co (344 +/- 15.9 kJ x kg(-0.40) x d(-1)) than in the HP group (377 +/- 12.4 kJ. x kg(-0.40) x d(-1)). During the first 40 d of MAIN, the energy requirement for weight maintenance was 398.7 +/- 9.7 kJ.kg(-0.40) x d(-1) for both groups, corresponding to 73% of the NRC recommendation. The required energy gradually increased in both groups (P < 0.05) but at a faster rate in HP; therefore, the energy consumption during the last 40 d of the MAIN was higher (P < 0.001) for the HP cats (533.8 +/- 7.4 kJ x kg(-0.40) x d(-1)) than for the control cats (462.3 +/- 9.6 kJ x kg(-0.40) x d(-1)). These findings suggest that HP diets allow a higher energy intake to weight loss in cats, reducing the intensity of energy restriction. Protein intake also seemed to have long-term effects so that weight maintenance required more energy after weight loss.

Topics: Animals; Body Composition; Cat Diseases; Cats; Dietary Proteins; Energy Intake; Female; Insulin; Leptin; Male; Nitrogen; Nutritional Requirements; Obesity; Weight Loss

Topics: Adipokines; Adiponectin; Animals; Cat Diseases; Cats; Humans; Insulin Resistance; Leptin; Obesity; Tumor Necrosis Factor-alpha

The effect of a 2-week administration of 75microg triiodothyronine (T3) on substrate oxidation, heat production, non-esterified fatty acids, and leptin was evaluated in eight lean (three females and five males) and eight obese (five females and three males) age-matched adult neutered cats. In addition, using real-time RT-PCR, expression of muscle and adipose tissue uncoupling proteins (UCP2 and UCP3), deiodinase 1 and 2 (D1; D2), and peroxisome proliferator-activated receptor (PPAR) alpha and gamma and peroxisome-proliferator-activator receptor-gamma co-activator 1alpha (PGC1) was examined. Compared to lean cats, obese cats had increased NEFA, leptin, UCP2, and D1mRNA in muscle and UCP3mRNA levels in fat, but lower heat production, and fat PPARs and PGC1. T3 administration increased thermogenesis and NEFA in lean and obese cats, and adipose tissue PPARgamma in lean cats. It also increased muscle D1 in lean and D2 in obese cats. The increase in muscle D2 was interpreted to be reflective of the reduced serum total T4 concentration following T3 suppression of the pituitary. No effect was seen on leptin, or UCP2 and 3. This shows that T3 regulates thermogenesis but not through changes in uncoupling protein expression. It also indicates that PPARs have an important role in the pathogenesis of obesity in cats.

Topics: Adipose Tissue; Animals; Cat Diseases; Cats; Fatty Acids, Nonesterified; Female; Gene Expression; Iodide Peroxidase; Ion Channels; Leptin; Male; Mitochondrial Proteins; Muscle, Skeletal; Obesity; Oxidation-Reduction; PPAR alpha; PPAR gamma; RNA, Messenger; Thermogenesis; Thyroxine; Transcription Factors; Triiodothyronine; Uncoupling Protein 2; Uncoupling Protein 3

A high concentration of dietary carbohydrate is suggested to increase the risk of obesity and diabetes mellitus in domestic cats. To evaluate this, food intake, body weight, fat mass and circulating adiposity-related factors were determined in twenty-four sexually mature (9-12 months) cats assigned to four six-cat dietary groups balanced for body weight and sex. The effect of dietary fat in exchange for carbohydrate at 9, 25, 44 and 64 % of metabolisable energy (ME) in a purified diet of constant protein:ME ratio was studied 13 weeks before and 17 weeks after gonadectomy (GX). Body weight did not significantly change among the cats before GX except for an increase of 17 (sem 5) % in cats given the highest-fat diet. Following GX, all groups gained body weight, and body fat mass was positively correlated (r 0.50; P < 0.04) with dietary fat percentage. Post-GX weight gains were much greater for females (+39 (sem 5) %) than males (+10 (sem 4) %). Plasma ghrelin concentration negatively correlated (P < 0.02) with dietary fat percentage and, before GX, was greater (P < 0.05) in females than males. Plasma insulin concentration increased with weight gain induced by high dietary fat. Plasma glucose, TAG and leptin concentrations were not affected by dietary fat percentage, GX or weight gain. These data provide evidence that in cats, high dietary fat, but not carbohydrate, induces weight gain and a congruent increase in insulin, while GX increases sensitivity to weight gain induced by dietary fat.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Composition; Castration; Cat Diseases; Cats; Dietary Carbohydrates; Dietary Fats; Energy Metabolism; Female; Ghrelin; Insulin; Leptin; Male; Obesity; Orchiectomy; Ovariectomy; Peptide Hormones; Sex Factors; Triglycerides; Weight Gain

To elucidate the impact of dietary influence on carbohydrate and lipid metabolism and on the development of diabetes mellitus in the carnivorous cat, a 3 weeks feeding trial was carried out on six sexually intact and six neutered adult male cats. The effects of two isonitrogenic diets, differing in carbohydrate and fat content, were investigated on plasma metabolite levels in a 24-h blood sampling trial. Plasma leptin concentrations were also determined at the beginning and at the end of the 24-h trial. Glucose and insulin response was measured in an i.v. glucose tolerance test. A 5 days long digestion trial was also performed, which revealed a high digestion capacity of both fat and carbohydrates in cats. The high fat diet induced a significant rise in the plasma triglyceride, FFA, beta-hydroxybutyrate and cholesterol concentration, while the elevation in the glucose level did not reach significance. In the glucose tolerance test no significant difference was found between the neutered and intact cats. However, independently of the sexual state, the cats on the high fat diet showed a slightly elongated glucose clearance and reduced acute insulin response to glucose administration. This is indicative of diminished pancreatic insulin secretion and/or beta-cell responsiveness to glucose. The results of this preliminary study may be the impetus for a long-term study to find out whether it is rather the fat rich ration than carbohydrate rich diet that is expected to impair glucose tolerance and thus might contribute to the development of diabetes mellitus in cats. Whether the alteration in glucose metabolism is due to altered leptin levels remains to be determined.

Topics: 3-Hydroxybutyric Acid; Animals; Blood Glucose; Case-Control Studies; Cat Diseases; Cats; Cholesterol; Diabetes Mellitus, Type 2; Diet; Dietary Carbohydrates; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Leptin; Male; Orchiectomy; Triglycerides

Leptin is a protein synthesized and secreted primarily by adipose tissue. The blood leptin concentration is known to reflect body fat content in rodents, humans and dogs, and thereby is useful for quantitative assessment of obesity. In the present study, we produced recombinant feline leptin in Escherichia coli transfected with feline leptin cDNA we cloned previously. The recombinant feline leptin with a molecular weight of 16 kDa induced phosphorylation of the signal transducers and activators of transcription 3 (STAT3) protein in the cells expressing rat leptin receptor. The anti-feline leptin antibody raised in rabbits reacted well to feline and human leptin and less to rodents' leptin in Western blot analysis. Sandwich enzyme-linked immunosorbent assay (ELISA) was developed, using rabbit anti-feline leptin antibody and recombinant feline leptin as a standard. In this ELISA system, cross-reactivity to human, rat and mouse leptin was 30.7%, 69.5% and 66.6%, respectively. The plasma leptin levels of 24 healthy cats were in a range from 0.3 to 29.7 ng/ml with the mean +/- SEM of 4.5 +/- 1.3 ng/ml, being positively proportional to body fat content. These results indicate that our ELISA system may be useful for assessment of obesity in cats.

Topics: Animals; Antibody Formation; Blotting, Western; Cat Diseases; Cats; CHO Cells; Cricetinae; Cricetulus; DNA-Binding Proteins; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Leptin; Obesity; Rabbits; Recombinant Proteins; Signal Transduction; STAT3 Transcription Factor; Trans-Activators

This study investigated relationships between plasma leptin, insulin concentrations, insulin sensitivity and glucose tolerance in lean and overweight cats. Leptin concentrations were measured in 16 cats during glucose tolerance tests before and after gaining weight, and after feeding a test meal in overweight cats. An important finding of this study is that in both lean (r=-0.79) and overweight (r=-0.89) cats, the higher the leptin concentrations, the more insulin resistant the cat, independent of the degree of adiposity. Leptin concentrations at baseline and after consuming a meal tended to be higher in overweight cats with glucose intolerance, compared to overweight cats with normal glucose tolerance, although the difference was not significant. After feeding the test meal to overweight cats in the early morning, plasma leptin concentrations initially decreased before subsequently rising to peak 15 h later, which coincided with late evening. The leptin peak occurred 9 h after the insulin peak following ingestion of the test meal. Importantly, this study suggests that increased leptin concentrations may contribute to the diminished insulin sensitivity seen in overweight cats. Alternatively, the compensatory hyperinsulinaemia found with insulin resistance in overweight cats could stimulate leptin production.

Topics: Animals; Blood Glucose; Body Composition; Cat Diseases; Cats; Energy Intake; Female; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Male; Obesity; Weight Gain

The present study was conducted to assess the body composition, leptin, and energy expenditure changes following gonadectomy in cats. Twenty-one females (12 intact and nine spayed) and 21 males (11 intact and 10 castrated) were used. Body weight was recorded. Serum plasma leptin was measured by radioimmunoassay and body composition and energy expenditure were assessed after injection of doubly labelled water. These results confirmed the gain in body weight and body fat following neutering and demonstrated a strong linear relationship between body fat and serum level of leptin. Energy expenditure decreased in castrated cats in comparison with intact ones. This study underlined the effect of gonadectomy as a major factor of obesity in cats and showed that the increase in circulating leptin reflected the amount of body fat. The present results provide further evidence that the regimen of gonadectomized cats should be carefully controlled to avoid excessive weight gain.

Topics: Adipose Tissue; Animals; Body Composition; Cat Diseases; Cats; Energy Metabolism; Female; Leptin; Male; Obesity; Orchiectomy; Ovariectomy; Radioimmunoassay; Weight Gain

The aims of our study were to determine a reference range for plasma leptin in healthy, normal-weight cats and to measure the effect of weight gain on plasma leptin levels. To increase our understanding of the association between leptin and feline obesity, we investigated the relationship between plasma leptin and measures of adiposity in cats. Twenty-six normal-weight cats were used to determine the reference range for feline leptin using a multispecies radioimmunoassay. In the second part of the study, plasma leptin concentrations were determined in 16 cats before and after approximately 10 months of spontaneous weight gain. Dual energy X-ray absorptiometry scans (DEXA) were performed after weight gain. The tolerance interval for plasma leptin concentrations was 0.92-11.9 ng/ml Human Equivalent (HE) with a mean concentration of 6.41+/-2.19 ng/ml HE. In part two of the study, 16 cats gained on average 44.2% bodyweight over 10 months. The percentage of body fat in obese cats ranged from 34.2 to 48.7%. Mean plasma leptin concentrations increased from 7.88+/-4.02 ng/ml HE before weight gain to 24.5+/-12.1 ng/ml HE after weight gain, (P<0.001). Total body fat and body fat per cent were the strongest predictors of plasma leptin in obese cats (r=0.8 and r=0.78, P<0.001, respectively). In conclusion, plasma leptin concentrations increased three-fold in cats as a result of weight gain and were strongly correlated with the amount of adipose tissue present. Despite elevated leptin levels, cats continued to eat and gain weight, suggesting decreased sensitivity to leptin. This investigation into the biology of leptin in cats may aid the overall understanding of the role of leptin and the development of future treatments to help prevent and manage feline obesity.

Topics: Absorptiometry, Photon; Adipose Tissue; Animals; Body Composition; Breeding; Cat Diseases; Cats; Female; Leptin; Male; Obesity; Radioimmunoassay; Reference Values; Weight Gain