Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner.

AIMS: Insulin is a potent stimulator of adipose tissue lipoprotein lipase (LPL). Logically, the postprandial period is therefore a privileged time of the day for the regulation of LPL by insulin in this tissue. It is not clear to what extent a defect such as insulin resistance could affect this regulation and contribute to postprandial, as well as fasting, hypertriglyceridaemia. The aim of the present protocol was to study the relationship between insulin resistance and LPL in adipose tissue and in plasma, in the particular context of the postprandial period. METHODS: For this study, 26 adult nondiabetic individuals (12 women and 14 men) with a wide range of whole-body insulin-mediated glucose uptake (as assessed with an insulin suppression test) were studied. An abdominal subcutaneous fat biopsy on one occasion, and post-heparin plasma on another occasion, were obtained 4 h into a standardized meal profile administered in the fasting state. RESULTS: Postprandial triglyceride excursions (evaluated by the incremental area under the curve during the metabolic meal profile) were inversely correlated to adipose tissue LPL mRNA levels (rho = -0.43, P < 0.03) as well as to adipose tissue LPL heparin-releasable activity (rho = -0.58, P < 0.01). Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test, a reflection of the degree of insulin resistance, were also negatively correlated to adipose tissue LPL mRNA (rho = -0.50, P < 0.02) and activity (rho = -0.56, P < 0.01). There was no correlation between plasma post-heparin LPL activity/mass and postprandial triglycerides nor with insulin resistance. CONCLUSION: Regulation of adipose tissue LPL is significantly affected in insulin-resistant individuals in the postprandial period. This presumed impaired effect of insulin on LPL postprandially could be an important contributor to the atherogenic dyslipidaemia described in insulin resistance syndrome.

Lipoprotein lipase steady-state mRNA levels are lower in human omental versus subcutaneous abdominal adipose tissue.

Adipose tissue synthesizes lipoprotein lipase (LPL), which helps in the postprandial clearance of triglyceride-rich lipoproteins. Because visceral adipose tissue is generally accepted as the most important metabolic tissue, we sought to verify whether there are regional differences in the expression of LPL. Samples of adipose tissue from subcutaneous and omental fat deposits were obtained from 20 adults undergoing surgery. Total adipose tissue LPL activity was measured using a conventional radioactive substrate assay. Steady-state levels of LPL mRNA were assessed using the very sensitive RNase protection assay technique with 18S ribosomal RNA as an internal control. A correlation was demonstrated between LPL activity levels in subcutaneous and omental tissue (r = .72; P < .01) and between mRNA levels at both sites (r = .47, P = .04). LPL mRNA levels were significantly lower in omental compared with subcutaneous depots (omental v subcutaneous, 1.7 +/- 0.7 v 2.1 +/- 0.7 arbitrary units [AU] over 18S, P < .05). In paired comparisons, LPL mRNA levels in omental adipose tissue were, on average, 20% +/- 7% (range, -57% to +9.0%) lower than the levels measured in subcutaneous adipose tissue (P < .05). In conclusion, these data suggest that subcutaneous adipose tissue is a reliable surrogate of the expression (activity and mRNA) of LPL in omental adipose tissue, even though omental depots express proportionally less LPL than subcutaneous depots.

The degree of hyperinsulinemia and impaired glucose tolerance predicts plasma leptin concentrations in women only: a new exploratory paradigm.

Plasma leptin has been shown to correlate positively with many indices of obesity, as well as insulin resistance. For a given body weight, the levels are higher in women than in men, but the reasons for this difference are not clear. Insulin has been shown to stimulate leptin production by adipose tissue in vivo and in vitro. Previous studies have reported that leptin levels are similar in diabetic and nondiabetic individuals. However, these studies were not performed in newly diagnosed diabetics, and other variables (such as gender) could have confounded the results. Therefore, the goal of the present cross-sectional study is to examine the effect of metabolic variables (such as glucose and insulin) on plasma leptin concentrations in men and women separately. We measured leptin levels in 48 subjects (17 with newly diagnosed type 2 diabetes mellitus, 13 with impaired glucose tolerance [IGT], and 18 normal individuals). The 3 groups were well matched for gender, age, and body mass index (BMI). When adjusted for the BMI and gender, a statistically significant gender-related difference in mean plasma leptin was observed across the 3 glucose tolerance subgroups (P < .03 by analysis of covariance [ANCOVA]). More specifically, plasma leptin levels were, on average, 44% lower in women with diabetes or IGT versus normal women (P < .02). No such between-group difference was observed in the men. In univariate analysis in the same female subgroup, plasma leptin correlated positively with fasting insulin (rs = +.43, P < .06) and negatively with 2-hour post-75-g glucose load plasma glucose concentration (rs = -.54, P < .02). In a multiple regression model controlling for the BMI in the female subgroup, circulating insulin and glucose concentrations 2 hours after the 75-g glucose load were good predictors of fasting plasma leptin (r = +.38, P = .02 and r = -.70, P < .001, respectively). Leptin levels in women appear to be influenced independently and to an important degree by ambient plasma glucose and plasma insulin concentrations. These findings suggest that the synthesis of leptin by adipose tissue is more susceptible to in vivo regulation by insulin and glucose in women than in men. Plasma leptin concentrations were also lower in women with IGT or type 2 diabetes versus normal women, suggesting that fasting and/or postprandial hyperglycemia interferes with the stimulatory effect of plasma insulin on the synthesis of leptin by adipose tissue in women only.