retinol-palmitate and Insulin-Resistance

The effects of variations in dietary carbohydrate and fat on various aspects of carbohydrate and lipoprotein metabolism were evaluated in 10 healthy, postmenopausal women. The two diets were isoenergetic, assigned in random fashion, and consisted (as a % of total energy) of 15% protein, 60% carbohydrate, and 25% fat (60%-carbohydrate diet) or 15% protein, 40% carbohydrate, and 45% fat (40%-carbohydrate diet). Fasting plasma triacylglycerol, very-low-density-lipoprotein (VLDL) triacylglycerol, and VLDL-cholesterol concentrations were higher (P < 0.05-0.001) after the 60%-carbohydrate diet, whereas high-density-lipoprotein (HDL) cholesterol was lower (P < 0.05). Plasma insulin and triacylglycerol concentrations were also higher (P < 0.001) from 0800 to 0000 with the 60%-carbohydrate diet than with the 40%-carbohydrate diet. In addition, when vitamin A was given with the noon meal, the ensuing concentrations of retinyl palmitate were also higher after ingestion of the 60%-carbohydrate diet. Resistance to insulin-mediated glucose disposal, quantified at baseline by determining the steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, insulin, and glucose, correlated with the incremental increases in postprandial concentrations of plasma glucose (r = 0.68, P = 0.06), insulin (r = 0.82, P < 0.02), triacylglycerol (r = 0.77, P < 0.05), and retinyl palmitate (r = 0.68, P = 0.06) and with the Sf > 400 triacylglycerol (r = 0.77, P < 0.05), Sf 20-400 triacylglycerol (r = 0.72, P < 0.05), and Sf > 400 retinyl palmitate (r = 0.75, P < 0.01) lipoprotein fractions. Because all of these changes would increase risk of ischemic heart disease in postmenopausal women, it seems reasonable to question the wisdom of recommending that postmenopausal women consume low-fat, high-carbohydrate diets.

Topics: Aged; Blood Glucose; Carbohydrate Metabolism; Cholesterol; Cholesterol, HDL; Diet, Fat-Restricted; Dietary Carbohydrates; Dietary Fats; Diterpenes; Female; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Middle Aged; Myocardial Ischemia; Postmenopause; Retinyl Esters; Risk Factors; Triglycerides; Vitamin A

Vitamin A is an essential nutrient with vital biological functions. The present study investigated the effect of different doses of vitamin A palmitate at different time intervals on thyroid hormones and glycemic markers.. Male rats were administrated vitamin A palmitate at different doses (0, 0.7, 1.5, 3, 6, and 12 mg/kg, oral) and samples were collected at different time intervals of 2, 4, and 6 weeks. The levels of vitamin A, thyroid hormones (T3, T4, and TSH), deiodinases (Dio1 and Dio3), glycemic markers (blood insulin and fasting glucose levels, HOMA IR and HOMA β), retinol-binding protein 4 (RBP4) and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were measured.. The findings demonstrated that long-term supplementation with high doses of vitamin A palmitate resulted in hypothyroidism (lower T3 and T4 levels and elevated TSH levels) as well as upregulation of Dio1 and Dio3 expression levels. This effect was associated with elevated glucose and insulin levels, enhanced HOMA IR, and decreased HOMA B index. In addition, prolonged vitamin A supplementation significantly increased RBP4 levels that upregulated the expression of PEPCK.. High doses of vitamin A supplementation increased the risk of hypothyroidism, modulated insulin sensitivity, and over a long period, increased the incidence of type 2 diabetes mellitus associated with oxidative stress and hepatitis.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Glucose; Hypothyroidism; Insulin; Insulin Resistance; Insulins; Iodide Peroxidase; Male; Phosphoenolpyruvate; Rats; Rats, Wistar; Thyroid Hormones; Thyrotropin; Vitamin A

Apolipoprotein AII (apoAII) transgenic (apoAIItg) mice exhibit several traits associated with the insulin resistance (IR) syndrome, including IR, obesity, and a marked hypertriglyceridemia. Because treatment of the apoAIItg mice with rosiglitazone ameliorated the IR and hypertriglyceridemia, we hypothesized that the hypertriglyceridemia was due largely to overproduction of very low density lipoprotein (VLDL) by the liver, a normal response to chronically elevated insulin and glucose. We now report in vivo and in vitro studies that indicate that hepatic fatty acid oxidation was reduced and lipogenesis increased, resulting in a 25% increase in triglyceride secretion in the apoAIItg mice. In addition, we observed that hydrolysis of triglycerides from both chylomicrons and VLDL was significantly reduced in the apoAIItg mice, further contributing to the hypertriglyceridemia. This is a direct, acute effect, because when mouse apoAII was injected into mice, plasma triglyceride concentrations were significantly increased within 4 h. VLDL from both control and apoAIItg mice contained significant amounts of apoAII, with approximately 4 times more apoAII on apoAIItg VLDL. ApoAII was shown to transfer spontaneously from high density lipoprotein (HDL) to VLDL in vitro, resulting in VLDL that was a poorer substrate for hydrolysis by lipoprotein lipase. These results indicate that one function of apoAII is to regulate the metabolism of triglyceride-rich lipoproteins, with HDL serving as a plasma reservoir of apoAII that is transferred to the triglyceride-rich lipoproteins in much the same way as VLDL and chylomicrons acquire most of their apoCs from HDL.

Topics: Animals; Apolipoprotein A-II; Chylomicrons; Diterpenes; Fatty Acids; Gene Expression Regulation; Hydrolysis; Insulin Resistance; Lipoproteins, VLDL; Liver; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; 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

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

We examined the relation between insulin resistance, plasma glucose and insulin responses to meals, lipoprotein lipase (LPL) activity, and postprandial lipemia in a population of 37 healthy nondiabetic individuals. Plasma glucose and insulin concentrations were determined at frequent intervals from 8 AM through midnight (breakfast at 8 AM and lunch at noon); resistance to insulin-mediated glucose disposal was determined by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of glucose, insulin, and somatostatin; LPL activity was quantified in postheparin plasma; and postprandial concentrations of triglyceride (TG)-rich lipoproteins were assessed by measuring the TG and retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20 to 400 lipoprotein fractions. Significant simple correlation coefficients were found between various estimates of postprandial lipemia and SSPG (r = .38 to .68), daylong insulin response (r = .37 to .58), daylong glucose response (r = .10 to .39), and LPL activity (r = -.08 to -.58). However, when multiple regression analysis was performed, only SSPG remained independently associated with both postprandial TG and retinyl palmitate concentrations. These data provide evidence that insulin resistance plays an important role in regulating the postprandial concentration of TG-rich lipoproteins, including those of intestinal origin.

Topics: Adult; Aged; Blood Glucose; Diterpenes; Eating; Female; Heparin; Homeostasis; Humans; Hyperinsulinism; Insulin Resistance; Intestinal Mucosa; Lipids; Lipoprotein Lipase; Lipoproteins; Liver; Male; Middle Aged; Retinyl Esters; Triglycerides; Vitamin A