salicylates and Weight-Gain

The efficacy of bacitracin methylene disalicylate (BMD) in the management of necrotic enteritis (NE) when fed in combination with narasin was investigated in a floor-pen study of 2,000 broiler chickens using a Clostridium perfringens inoculum challenge model. Treatments consisted of 1) nonchallenged-nonmedicated; 2) challenged-nonmedicated; 3) challenged-narasin (70 ppm); 4) challenged-BMD (55 ppm); 5) challenged-narasin (70 ppm) + BMD (55 ppm). Medication was provided in the feed from Day 0 to trial termination on Day 41. C. perfringens challenge occurred from Day 14 to 16. BMD and narasin, fed alone and in combination, reduced (P < 0.05) mortality due to NE when compared to challenged-nonmedicated birds. NE lesion scores (Days 0 through 41) were lower among birds fed BMD and narasin, alone and in combination, compared to challenged-nonmedicated birds. Improvements in NE mortality and NE lesion scores were greatest for the BMD + narasin-medicated birds, followed by the BMD-alone, and then narasin-alone treated birds. BMD and narasin, alone and in combination, provided improvements (P < 0.05) in average daily gains over the entire study (Days 0 to 41). The results of this study demonstrate the effectiveness of BMD and narasin in the management of NE in broiler chickens.

Topics: Animals; Anti-Bacterial Agents; Bacitracin; Chickens; Clostridium Infections; Clostridium perfringens; Enteritis; Male; Necrosis; Poultry Diseases; Pyrans; Salicylates; Weight Gain

Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin. Unfortunately, metformin does not protect against antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be salsalate, the prodrug of salicylate, which acts synergistically with metformin to improve indices of glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of salsalate, metformin and a combination of both drugs, on weight gain and indices of metabolic health in female mice treated with the antipsychotic, olanzapine. Herein we demonstrate that salsalate was equally as effective as metformin in protecting against olanzapine induced weight gain and liver lipid accumulation with no additional benefit of combining both drugs. Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Female; Glucose; Humans; Lipids; Metformin; Mice; Olanzapine; Salicylates; Weight Gain

Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We found that salsalate attenuated and reversed high-fat diet-induced weight gain, in particular fat mass accumulation, improved glucose tolerance, and lowered plasma triglyceride levels. Mechanistically, salsalate selectively promoted the uptake of fatty acids from glycerol tri[(3)H]oleate-labeled lipoprotein-like emulsion particles by brown adipose tissue (BAT), decreased the intracellular lipid content in BAT, and increased rectal temperature, all pointing to more active BAT. The treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by the inhibition of cAMP-dependent protein kinase (PKA). In conclusion, salsalate activates BAT, presumably by directly activating brown adipocytes via the PKA pathway, suggesting a novel mechanism that may explain its beneficial metabolic effects in type 2 diabetes patients.

Topics: Adipose Tissue, Brown; Animals; Dietary Fats; Drug Administration Schedule; Glucose; Lipid Metabolism; Male; Mice; Mice, Transgenic; Obesity; Salicylates; Weight Gain

The intestine of the newly hatched chick is immature at hatch. Yeast contains nucleotides and β-glucans that enhance intestinal development and chick growth. Accordingly, a 14-d experiment was conducted to evaluate the efficacy of a novel yeast product and bacitracin methylene disalicylate in enhancing early growth and intestinal maturation in chicks obtained from young (26-27 wk old) and old (58 to 59 wk old) breeder hens. Chicks (384) were randomly assigned to 8 dietary treatments. Treatment 1 (YH) consisted of chicks, from young hens, fed corn-soybean meal (SBM) diet alone. Treatment 2 (YHB) consisted of chicks, from young hens, fed corn-SBM basal into which BMD was added at 0.055 g/kg. Treatment 3 (YHE) consisted of chicks, from young hens, fed corn-SBM basal into which yeast extract (YE) was added at 0.075% level. Treatment 4 (YHED) consisted of chicks, from young hens, fed corn-SBM basal into which YE was added at 0.15% level. Treatments 5 (OH), 6 (OHB), 7 (OHE), and 8 (OHED) consisted of chicks from old hens fed diets similar to those given to YH in treatments 1, 2, 3, and 4, respectively. Growth performance (body weight gain and feed conversion ratio) was evaluated on d 7 and 14. Intestinal tissue samples were also analyzed for alkaline phosphatase (ALP) activity as an indicator of intestinal maturation on d 4 and 13 of experiment. Results showed that by d 14 of experiment, only BMD treatments (YHB and OHB) improved body weight gain (P < 0.05). However, the body weight gains of chicks in the yeast-supplemented treatments (YHE, YHED, OHE, and OHED) were statistically similar (P > 0.05) to those of the BMD treatments. Ileal ALP activity was consistently enhanced by BMD and yeast product supplemented at 0.075% of the diet. It was concluded that antibiotic BMD and our novel yeast product supplemented at 0.075% of the diet improved early chick growth and maturation of the ileal segment of the small intestine.

Topics: Aging; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Bacitracin; Chickens; Diet; Dietary Supplements; Female; Intestines; Salicylates; Weight Gain; Yeasts

Disalicylic acid derivatives with stilbene and bis-styrylbenzene skeleton were synthesized as PTP1B inhibitors. The most potent in this series exhibited a submicromolar IC(50) value. One of the compounds 7b was tested in an animal model for its efficacy as an anti-diabetic or an anti-obesity agent. In feeding compound 7b to diet-induced obese mice, no significant differences in weight gain and food consumption were observed between the drug-treated and the obese control mice. However, 7b significantly lowered the fasting glucose level and improved the glucose tolerance in the obesity-induced diabetic mice.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Disease Models, Animal; Fasting; Glucose Tolerance Test; Hyperglycemia; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Salicylates; Stilbenes; Structure-Activity Relationship; Styrenes; Weight Gain

Methylenedisalicylic acid derivatives were synthesized and their inhibitory activities against protein tyrosine phosphatases (PTPases) examined. Two of the compounds, 8 and 9, showed K(i) values of 9.4 and 6.3microM against PTP1B, 4- and 7-fold lower values compared to those against TC-PTP. They were reversible and slow-binding inhibitors against PTP1B. When compound 8 was fed to a mouse model, the weight gain and adipocyte fat storage induced by a high-fat-diet were significantly suppressed.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Diet; Disease Models, Animal; Mice; Mice, Inbred C57BL; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Salicylates; Weight Gain

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Duodenal Ulcer; Esophagitis, Peptic; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Omeprazole; Organometallic Compounds; Penicillins; Prospective Studies; Risk Factors; Salicylates; Sex Factors; Weight Gain