retinol-palmitate and Obesity

T helper (Th)1/Th2 immune response has been linked to obesity-related immune disorders. It has been proven that retinoid active derivates improve immunity via regulating Th1/Th2 balance. However, there is not a well-identified report of direct effect of vitamin A on Th1/Th2 balance in obesity. The present study aimed to investigate the possible role of vitamin A on serum Th1/Th2 response in obese women.. A randomized double-blind placebo-controlled trial was conducted on 84 obese (n = 56; body mass index [BMI] 30-39.9 kg/m(2)) and nonobese (n = 28; BMI 18.5-24.9 kg/m(2)) women. Obese women were randomly allocated to receive either vitamin A (retinyl palmitate 25,000 IU/d) or placebo. Nonobese women also received 25,000 IU/d retinyl palmitate. Anthropometric variables were assessed and serum interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, and IL-13 were analyzed before and 4 months after intervention.. Vitamin A treatment significantly reduced serum concentrations of IL-1β in obese vitamin A-treated subjects (from 3.58 ± 0.36 to 2.45 ± 0.23 pg/ml, p < 0.006). Serum concentrations of IL-4 and IL-13 were also reduced in obese and nonobese vitamin A-treated subjects (p < 0.05). A significant reduction in IL-1β/IL-4 ratio in the obese vitamin A-treated group was also observed (p = 0.03).. Decline in serum concentrations of IL-1β and IL-1β/IL-4 ratio in obese women suggests that vitamin A is capable of regulating the immune system and possibly reducing the risk of autoimmune disease in this group. Further studies are needed to explore the possible underlying mechanisms.

Topics: Adult; Body Mass Index; Cytokines; Dietary Supplements; Diterpenes; Double-Blind Method; Female; Humans; Interleukin-13; Interleukin-1beta; Interleukin-4; Obesity; Retinyl Esters; Th1-Th2 Balance; Tumor Necrosis Factor-alpha; Vitamin A

There are few therapeutic treatments established for cellulite.. We studied the response of intense pulsed light (IPL) treatment with or without a compounded prescription retinyl-based cream on a small group of patients who had visible cellulite present on the buttocks and thigh regions.. Twenty patients were selected to complete a 12-week course of IPL treatment either with or without a retinyl-based cream. Assessment was based on visual evaluation, photographs, skin ultrasounds, and patient satisfaction.. Fifteen (75%) completed the study, and nine (60%) had a self-improvement rating of >or= 50%. Seven (78%) of nine patients used IPL/cream. Of the remaining six (40%) completing the study, four (27%) had self-improvement ratings of 25-50% and two (13%; IPL only) were considered treatment failures with a rating of 10-25%. Both IPL/cream and IPL-only groups exhibited an improvement in the smoothness of the affected area even following weight gain. Skin ultrasounds confirmed an increase in the deposition of collagen. During an 8-month phone follow-up, 8 (67%) of 12 responding reported the same or improved results.. IPL treatment with or without a retinyl-based cream can improve the appearance of peau d'orange cellulite, though the cream may augment cosmetic improvement. This approach is well tolerated, has minimal side effects, and is accompanied by a high degree of patient satisfaction.

Topics: Adipose Tissue; Adult; Antioxidants; Diterpenes; Female; Follow-Up Studies; Humans; Laser Therapy; Lasers; Middle Aged; Obesity; Patient Satisfaction; Pilot Projects; Retinyl Esters; Treatment Outcome; Vitamin A

Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P < .01). In contrast, the renal retinol concentrations of GK rats increased by 70% (P < .01). However, expression of RARβ in the kidney, which was induced in a retinoic acid-dependent manner, was downregulated by 90% (P < .01) in GK rats. In conclusion, diabetes and obesity affected retinol metabolism differently, and the effects were different in different peripheral tissues. The impact of HFD may be limited to the storage of hepatic vitamin A as retinyl palmitate. In particular, our data indicate that renal retinoic acid production might represent an important target for the treatment of type 2 diabetes mellitus.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Fats; Diterpenes; Down-Regulation; Insulin; Kidney; Liver; Male; Obesity; Rats; Rats, Wistar; Receptors, Retinoic Acid; Retinol-Binding Proteins, Plasma; Retinyl Esters; Vitamin A

Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats.. Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks.. Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyltransferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet.. Chronic feeding of a vitamin A-enriched diet in hypercholesterolemic obese rats normalizes the plasma HDL-C level and presumably improves RCT, with an effective dose of 52 mg/kg diet. Further studies should focus on the pharmacological potential of vitamin A supplementation to correct an abnormal human obesity-associated lipoprotein metabolism.

Topics: Animals; Antioxidants; Biological Transport; Cholesterol; Diet; Diterpenes; Humans; Hypercholesterolemia; Liver; Male; Obesity; Rats; Rats, Mutant Strains; Retinyl Esters; Thinness; Vitamin A

High-dose vitamin A influences glucose and lipid profile; however, the possible effects of moderate doses (25,000 IU/d) are conflicting. We aimed to compare the effect of vitamin A supplementation on several anthropometric and biochemical variables between obese and non-obese women.. This study was performed on 84 women among whom 56 were obese (body mass index [BMI] 30-35 kg/m(2)) and 28 were non-obese (BMI 18.5-24.9 kg/m(2)). Obese women were randomly divided into two groups: one group received 25,000 IU/d retinyl palmitate and another group received placebo. The third group was age-matched non-obese women who received 25,000 IU/d retinyl palmitate. At baseline and four months after intervention, fasting blood glucose (FBG), lipid profile, C-reactive protein (CRP) and liver enzymes were evaluated.. Baseline concentrations of serum FBG and triglyceride in the obese vitamin A-treated group were significantly higher compared with the other groups (P = 0.004 and 0.007, respectively). A significant increase in serum FBG (P = 0.026), total cholesterol (TC) (P = 0.004) and low-density lipoprotein cholesterol (LDL-C) (P = 0.016) in the non-obese group and a significant decrease in serum high-density lipoprotein cholesterol (HDL-C) (P = 0.001) in the obese group was observed. Serum CRP increased significantly in the obese vitamin A-treated group (P = 0.03) and serum aspartate transaminase increased significantly in the obese and non-obese groups after vitamin A supplementation (P = 0.008 and 0.001, respectively).. Treatment with 25,000 IU/d vitamin A induced a mild elevation in serum lipids, CRP and liver enzymes in obese and non-obese women. Considering the other information about possible side-effects of excess vitamin A, use of vitamin A in this dose and duration should be considered with caution.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Blood Glucose; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Diterpenes; Female; Humans; Insulin; Liver; Middle Aged; Obesity; Random Allocation; Retinyl Esters; Triglycerides; Vitamin A

Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 +/- 0.6 vs. 0.8 +/- 0.2, respectively. Plasma apolipoprotein B(48) (apoB(48)) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB(48) was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB(48) and RP curves (IAUC) were both significantly greater in obese subjects (apoB(48): 97 +/- 17 vs. 44 +/- 12 microg.ml(-1). h; RP: 3,120 +/- 511 vs. 1,308 +/- 177 U. ml(-1). h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 +/- 0.6 vs. 2.8 +/- 0.8 mM. h, P < 0.06). Moreover, peak postprandial triglyceride was delayed by approximately 2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 +/- 15.07 vs. 38.9 +/- 4.6 ng LDL bound/microg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesis in viscerally obese, insulin-resistant subjects may in part reflect delayed clearance of postprandial lipoprotein remnants.

Topics: Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Body Constitution; Body Mass Index; Cholesterol; Cholesterol, HDL; Chylomicrons; Dietary Fats; Diterpenes; Food; Humans; Hyperlipidemias; Insulin; Insulin Resistance; Kinetics; Lipase; Lipoproteins, LDL; Male; Middle Aged; Obesity; Receptors, LDL; Retinyl Esters; Triglycerides; Viscera; Vitamin A

The oral fat load tests used to study postprandial lipemia are complex and costly and time consuming. A simplified fat load test could be more convenient and more appropriate in routine clinical practice because of the number of lipid determinations required.. We evaluated the capacity of a postprandial test model that reduced the number of blood samples taken in thirty three normal weight controls and 17 normotriglyceridemic obese patients (study 1), 10 normolipidemic type 2 diabetic patients and 7 healthy controls (study 2), and 10 hyperlipidemic type 2 diabetic patients studied before and after hypolipidemic therapy (study 3). Blood samples were taken before and up to 8 hours after giving the oral fat load containing retinol. Triglyceride (TG) and retinyl palmitate (RP) concentrations in the plasma, chylomicrons (CM) and non-chylomicron (nCM) fractions were measured. Postprandial lipid responses using conventional area under the curves (AUCc using 5 to 7 lipid determinations) were compared to a 3-point test that uses only three sample points to predict the area under the curve (AUCp: triglycerides at T0, triglycerides at average peak-time (T4), and triglycerides at T8).. The AUCc and AUCp for triglycerides and retinyl palmitate were highly correlated in each of the groups and whatever the lipid subfraction (r=0.664 - 0.995, p<0.0001). When incremental AUC (iAUC) were used, the coefficients of correlation for triglycerides remained highly significant between iAUCc and iAUCp (r=0.718 - 0.979, p<0.01 - 0.0001). The same trend of differences was found between cases and controls when AUCp was used instead of AUCc. The means of differences between AUCc and AUCp for triglyceride values were small (0.34 - 0.74 mmol/L.h), and the confidence intervals were acceptable considering the range of the AUCs values (5.60 to 79.8 mmol/L.h for plasma triglycerides).. We found that data obtained with a simplified model of AUC using only 3 points to analyse postprandial lipemia are well correlated with those obtained by conventional AUC, and that the AUCp allows to the same conclusions as AUCc when healthy subjects were compared to patients with altered postprandial metabolism. Thus AUCp may be a good evaluation of the AUCc, and the simplified 3-point protocol may well be used and suitable for studies on large groups of subjects who are eligible for an oral fat load test.

Topics: Area Under Curve; Body Mass Index; Body Weight; Chylomicrons; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Female; Humans; Hypertriglyceridemia; Hypoglycemic Agents; Male; Models, Biological; Obesity; Postprandial Period; Reference Values; Retinyl Esters; Time Factors; Triglycerides; Vitamin A

Although there are changes in the postprandial lipid responses of obese patients, these are closely associated with high fasting triglycerides (TG). This study of 17 normotriglyceridemic, normoglucose-tolerant android obese subjects (body mass index, BMI = 34.3 +/- 3.1 kg/m2) and 33 normal-weight controls (BMI = 21.8 +/- 1.6 kg/m2) was done to examine their postprandial responses to an oral fat loading test containing retinol (890 calories, 85% fat) and to evaluate the possible association between clinical and biological features of obesity and/or insulin resistance and postprandial lipemia.. Blood samples were taken before giving the fat load and at 2,3,4,5,6 and 8 h after it. Insulin sensitivity was assessed using HOMA, and TG and retinyl palmitate (RP) in the plasma, chylomicrons and non-chylomicron fractions were measured each time.. The areas under the curves (AUC) of chylomicron TG for the obese and controls were not different, indicating adequate lipolytic activity. By contrast, the AUC for non-chylomicron TG was significantly greater in the obese than in the controls (512 +/- 135 vs 429 +/- 141 mmol/lmin, P < 0.01). In addition, the AUC for RP in this same fraction was significantly lower in the obese than in the controls (103 +/- 55 vs 157 +/- 88 mg/l min, P < 0.05), suggesting that the TG from endogenous lipoproteins accounted for most of the increase in TG in the non chylomicron fraction. Parameters related to obesity showed no relationship with these postprandial abnormalities, whereas HOMA, which discriminated between the groups, partly explained (r2= 23%, P < 0.01) the significant increase in non-chylomicron TG.. Android obese patients with a fasting TG in the normal range and not different from the fasting TG of lean controls had an abnormal postprandial lipemia response, indicated by a significantly greater TG in the non-chylomicron subfraction than in controls. These alterations may be partly due to postprandial changes in endogenous lipoproteins as a consequence of insulin resistance.

Topics: Adult; Area Under Curve; Blood Glucose; Case-Control Studies; Diterpenes; Eating; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Obesity; Postprandial Period; Regression Analysis; Retinyl Esters; Triglycerides; Vitamin A

Postprandial hyperlipidemia is frequently accompanied with intra-abdominal visceral accumulation in human subjects. We have found that the decreased lipoprotein lipase (LPL) mass and activity is negatively associated with the amount of visceral fat accumulation. Here, we studied the postprandial hyperlipidemia using the OLETF rat, a model with visceral obesity, in order to clarify the molecular mechanism causing postprandial hyperlipidemia accompanied with visceral obesity. At the same age of 32 weeks, the OLETF rats showed obviously higher plasma leptin, total cholesterol, triglyceride, and HDL-cholesterol levels than the control LETO rats, although the plasma glucose level was not significantly different. Fat-loading test revealed the delayed metabolism of exogenous fat in the OLETF rats compared to the LETO rats, similar to human subjects with visceral obesity. In the obese rats, plasma levels of LPL mass and activities were 60 and 49% of control rats. The expression of LPL gene was decreased in subcutaneous adipose tissues and skeletal muscle of OLETF rats to 40 and 52% compared to those of LETO rats. In OLETF rats, plasma tumor necrosis factor-alpha (TNF-alpha) and insulin levels were increased to 2.0- and 2.3-folds compared to those in control rats. Furthermore, plasma insulin and TNF-alpha levels in OLETF rats were negatively correlated with the expression levels of LPL gene in subcutaneous fat and muscle. These results indicate that decreased LPL mass and activity in the animal model with visceral obesity is possibly caused by decreased expression of LPL gene in tissues mediated by the increased levels of insulin and TNF-alpha. The different expression of LPL gene in tissues associated with the increased levels of insulin and TNF-alpha possibly elucidate the underlying mechanisms involving the postprandial hyperlipidemia observed in visceral obesity.

Topics: Adipose Tissue; Animals; Blood Glucose; Blotting, Northern; Body Weight; Cholesterol; Cholesterol, HDL; Cloning, Molecular; Disease Models, Animal; Diterpenes; Humans; Hyperlipidemias; Insulin; Leptin; Lipoprotein Lipase; Male; Muscle, Skeletal; Obesity; Rats; Rats, Long-Evans; Retinyl Esters; RNA, Messenger; Time Factors; Tissue Distribution; Triglycerides; Tumor Necrosis Factor-alpha; Vitamin A

Individuals with obesity, in particular those with intra-abdominal visceral fat accumulation, are known to have various complications, such as hyperlipidaemia, impaired glucose tolerance, hyperinsulinaemia and hypertension, leading to the development of coronary heart disease. Post-prandial hyperlipidaemia has repeatedly been shown to be an independent risk factor for coronary heart disease. The aim of the present study was to investigate post-prandial lipoprotein metabolism in subjects with excessive visceral fat accumulation.. Eighty-three patients (52 men, 31 women) [average age 48 +/- 14 years; mean body mass index (BMI) 25 +/- 5 kg m-2] were recruited to the study. Visceral (or subcutaneous) fat accumulation was analysed as areas of fat deposition by computerized tomography at the umbilicus level. After a 12-h overnight fast, oral vitamin A and a fatty meal (40 g m-2 fresh cream containing 50 000 units m-2 vitamin A) were administered to these subjects. The concentration of retinyl palmitate (RP) was measured by high-performance liquid chromatography.. The visceral fat area (V) was positively correlated with plasma triglyceride (TG) 0, 2, 4 and 6 h after fat loading and with plasma RP 0, 4 and 6 h after fat loading. The BMI did not show any correlation with plasma TG and RP at any point. The visceral fat area was positively correlated with the RP area under the curve (AUC) in the serum from the subjects [V vs. RP AUC: n = 83, r = 0.327, P = 0.013]. The BMI of the subjects did not show any correlation with the RP AUC (r = 0.021, P = 0.85).. These results suggest that post-prandial lipid metabolism is impaired in subjects with intra-abdominal visceral fat accumulation, irrespective of BMI, leading to the development and progression of coronary atherosclerosis.

Topics: Abdomen; Adipose Tissue; Adult; Aged; Anticarcinogenic Agents; Apolipoproteins E; Body Mass Index; Dietary Fats; Diterpenes; Female; Humans; Hyperlipidemias; Lipoprotein Lipase; Male; Middle Aged; Obesity; Phenotype; Postprandial Period; Regression Analysis; Retinyl Esters; Triglycerides; Viscera; Vitamin A

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with postprandial lipoprotein clearance defects that are correlated with the fasting hypertriglyceridemia widely observed in NIDDM patients. The aim of this study was to determine if such postprandial disturbances are found in NIDDM patients strictly normotriglyceridemic in the fasting state, and if the apolipoprotein E (apo E) polymorphism influences postprandial metabolism of intestinally derived lipoproteins. The vitamin A-fat loading test was used in 18 normotriglyceridemic NIDDM patients and seven normotriglyceridemic obese controls, and postprandial triglyceride (TG) and retinyl palmitate (RP) concentrations were evaluated in total plasma, and in the chylomicron (Sf > 1,000) and nonchylomicron (Sf < 1,000) fractions isolated by ultracentrifugation. NIDDM patients exhibited an amplified response of both TG and RP as compared with obese controls in the three fractions. Incremental TG response to the oral fat load was strongly correlated with fasting TG level (r = .80, P < .0001) in the whole study population. Postprandial lipoprotein profiles were distinguished in NIDDM patients according to apo E phenotype: despite normal fasting TG levels in E3/3 (n = 6), E2/3 (n = 6), and E3/4 (n = 6), postprandial RP response was twofold to threefold higher in E2/3 and E3/4 patients than in the common E3/3 phenotype. Contrasting lower postprandial TG increment and lower fasting and postprandial high-density lipoprotein (HDL) and HDL3 cholesterol levels were observed in E3/4 versus E3/3 patients, possibly reflecting modifications in lipid content of the postprandial lipoproteins driven by a differential lipid transfer activity depending on apo E isoform. These data indicate an enhanced postprandial lipemia in normotriglyceridemic NIDDM patients, and demonstrate the influence of apo E polymorphism on their lipoprotein clearance. Postprandial alterations of lipoprotein remnants may thus accelerate atherogenesis even in normotriglyceridemic NIDDM patients.

Topics: Adult; Apolipoproteins E; Cholesterol, HDL; Chylomicrons; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Eating; Female; Humans; Lipoproteins; Lipoproteins, HDL; Male; Middle Aged; Obesity; Phenotype; Polymorphism, Genetic; Retinyl Esters; Triglycerides; Vitamin A

Blood lipid alterations after a fatty meal may be atherogenic, but there is little information regarding their associations with disease independent of fasting lipids. Asymptomatic atherosclerosis cases (n = 229) and 373 control subjects free of atherosclerosis, as defined by carotid intima-media thickness on ultrasound images, were given a fatty meal with vitamin A, followed by 3.5- and 8-hour measurements of triglycerides (TGs), TG-rich lipoprotein TGs, apoproteinB48, and retinyl palmitate. Among white men and women but not among blacks, case status was associated with greater postprandial responses of TGs and TG-rich lipoprotein TGs, but only in nonobese persons (body mass index < 30 kg/m2). The associations were strong and significant after controlling for coronary risk factors (odds ratio, approximately 2.0) and fasting TGs (odds ratio, 1.5). Associations with other postprandial lipid measurements did not persist after controlling for fasting lipids. Elevated postprandial TGs appear to be an independent risk factor for carotid intimal thickening in nonobese whites. The lack of such a relation in obese subjects and the lipid profile they manifest suggest that postprandial TGs must be accompanied by accumulation of TG-rich lipoprotein remnants to be atherogenic.

Topics: Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Black People; Carotid Artery Diseases; Carotid Stenosis; Coronary Disease; Dietary Fats; Diterpenes; Female; Humans; Male; Middle Aged; Obesity; Retinyl Esters; Triglycerides; Vitamin A; White People