Postprandial plasma adiponectin decreases after glucose and high fat meal and is independently associated with postprandial triacylglycerols but not with -- 11388 promoter polymorphism

Adiponectin is discussed to regulate energy balance and insulin sensitivity. Several studies indicated an association of fasting adiponectin with parameters of the metabolic syndrome. We investigated postprandial adiponectin release and its relation to traits of the metabolic syndrome. Serum adiponectin concentration after an oral glucose tolerance test and after ingestion of a standardised mixed, fat-containing meal in 110 male non-diabetic subjects was assessed. Fasting and postprandial adiponectin and the decrease of adiponectin were correlated with anthropometric and metabolic parameters. Subjects were genotyped for adiponectin - 11 388 G/A promoter single nucleotide polymorphism. Adiponectin slightly decreased after both test meals. A significant decrease was attained 5 and 6 h after the lipid load and 2 h after the glucose load. Particularly, the mixed meal postprandial adiponectin showed stronger correlations with most traits of the metabolic syndrome than fasting adiponectin: postprandial adiponectin with HDL (r 0.30) v. fasting adiponectin with HDL (r 0.23); with postprandial insulin (area under the curve): r - 0.20 v. r - 0.16; with fasting insulin: r 0.10 v. r 0.14; with BMI: r - 0.23 v. r - 0.20; with waist: r - 0.18 v. - 0.16; with systolic blood pressure: r - 0.14 v. r - 0.12; with diastolic blood pressure: r - 0.18 v. r - 0.15. In multivariate analysis, postprandial TAG were the only independent predictor of adiponectin. There was no significant association of adiponectin, NEFA and TAG with - 11 388 G/A adiponectin promoter polymorphism. Our findings favour the interpretation that postprandial adiponectin has the strongest and independent associations to postprandial TAG metabolism.     

Polymorphism in the PPARgamma2 and beta2-adrenergic genes and diet lipid effects on body composition, energy expenditure and eating behavior of obese women

In order to evaluate the effect of polymorphism in the PPARgamma2 and beta2-adrenergic genes and diet lipids on body composition, energy expenditure and eating behavior of obese women, 60 subjects were submitted to anthropometric, biochemical, dietary, molecular, basal and postprandial metabolism (indirect calorimetry) and eating behavior (visual analog scale) evaluation. Fat and saturated fatty acid (SFA) high diet was used to assess postprandial metabolism. The frequency of Pro12Pro/Gln27Gln, Pro12Pro/Gln27Glu, Pro12Pro/Glu27Glu and Pro12Ala/Gln27Glu genotypes was 35.71%, 30.37%, 23.21% and 10.71%, respectively. These values were not significant (p>0.05) for the dietary, anthropometric, biochemical and metabolic parameters. The Pro12Ala/Gln27Glu group was found to present greater energy used in postprandial period (EUPP). The presence of the PPARgamma2 gene variant, independent of beta2-adrenergic gene polymorphism, resulted in fat oxidation increase. Also, this group presented higher satiety, compared to the Pro12Pro/Gln27Gln group. The presence of the variant alleles in the PPARgamma2 gene suggests benefits in food intake control.     

Impact of Prol2Ala variant in the peroxisome proliferator-activated receptor (PPAR) gamma2 on obesity and insulin resistance in Japanese Type 2 diabetic and healthy subjects

The peroxisome proliferator-activated receptor (PPAR) gamma is an important regulator of adipocyte differentiation and a modulator of intracellular insulin-signaling events. We examined the roles of the Pro12Ala variant of PPAR gamma2 in obesity and insulin resistance in 402 Japanese patients with type 2 diabetes and 116 control subjects. Among the diabetes subjects, the Pro12Pro homozygotes showed significantly higher body mass index (BMI) than those with the Pro12Ala variant (p = 0.020), while there was no association between genotype and BMI in the controls. Furthermore, diabetic subjects with Pro12Pro showed significantly higher fat body mass index (FBMI) than those with Pro12Ala (p = 0.016), while no association between genotype and lean body mass index (LBMI) was observed. Regarding insulin resistance, there was no difference in the HOMA index or in clamp index between Pro12Ala and Pro12Pro variants. These data suggest that the Pro12Ala polymorphism of PPAR gamma2 does not influence insulin resistance but body composition in Japanese diabetic subjects.     

Pro12Ala polymorphism of the PPARG2 gene is associated with type 2 diabetes mellitus and peripheral insulin sensitivity in a population with a high intake of oleic acid

Activation of the PPAR gamma 2 gene (PPARG2) improves the action of insulin and its lipid metabolism. We examined the association between Pro12Ala polymorphism of PPARG2, type 2 diabetes mellitus (DM2), and peripheral insulin sensitivity in a population with a high intake of oleic acid. A cross-sectional, population-based study was undertaken in Pizarra, a small town in the province of Malaga in southern Spain. A total of 538 subjects, aged 18-65 y, were selected randomly from the municipal census. All subjects underwent a clinical, anthropometrical, and biochemical evaluation, including an oral glucose tolerance test and Pro12Ala polymorphism of PPARG2. Insulin resistance was measured by homeostasis model assessment. Those subjects with the Ala-12 allele had an odds ratio for impaired fasting glucose of 0.55, for impaired glucose tolerance of 0.59, and for DM2 of 0.30. The intake of monounsaturated fatty acids (MUFA) contributed to the variance of the homeostasis model assessment insulin resistance index (HOMA IR) (P = 0.04), with a 2-way interaction between the Ala-12 allele of PPARG2 and the intake of MUFA (P = 0.005). The results suggest the existence of an interaction between Pro12Ala polymorphism of PPARG2 and dietary MUFA, such that obese people with the Ala-12 allele have higher HOMA IR values, especially if their intake of MUFA is low.     

Association of pro12Ala polymorphism in the peroxisome proliferative-activated receptor gamma2 gene with obesity and hypertension in Korean women

This study examined whether the Pro12Ala polymorphism of the PPARgamma2 gene is associated with obesity, hypertension and cardiovascular risk profiles in Korean adult women. We studied 129 Korean women (aged 42.71 +/- 8.56 y) who were divided into 2 groups as a Pro12Pro homozygous group and a Pro12Ala heterozygous or Ala12Ala homozygous group based upon PPARy2 genotype. Anthropometric parameters, blood pressure, abdominal fat area and blood lipid profiles were compared between the 2 groups, and the association of Ala allele frequency in PPARgamma2 gene with obesity or hypertension was evaluated. Most anthropometric parameters and blood lipid profiles did not differ significantly between the genotypes. However, all variables of skinfold thickness, body circumference and abdominal fat area of Pro12Ala heterozygous were consistently higher compared to the Pro12Pro homozygous subjects without a significance differences. The hypertensive group had significantly higher (p = 0.004) Ala12 allele frequency than the normotensive group whereas allele frequencies did not differ significantly between the obese group and non-obese group. Ala allele carriers had a significantly higher risk of hypertension than non-carriers in logistic regression analysis. There was no evidence that the Ala allele can be regarded as an independent risk factor for obesity. In conclusion, all variables related to obesity showed a consistently higher trend in Pro12Ala heterozygous subjects compared to Pro12Pro homozygous subjects. Pro12Ala heterozygous subjects showed an increasing trend of elevated blood pressure compared to Pro12Pro homozygous subjects. Ala12 variant as well as BMI and TG were regarded as independent risk factors for hypertension in our subjects.     

Resistant starch consumption promotes lipid oxidation

BACKGROUND: Although the effects of resistant starch (RS) on postprandial glycemia and insulinemia have been extensively studied, little is known about the impact of RS on fat metabolism. This study examines the relationship between the RS content of a meal and postprandial/post-absorbative fat oxidation. RESULTS: 12 subjects consumed meals containing 0%, 2.7%, 5.4%, and 10.7% RS (as a percentage of total carbohydrate). Blood samples were taken and analyzed for glucose, insulin, triacylglycerol (TAG) and free fatty acid (FFA) concentrations. Respiratory quotient was measured hourly. The 0%, 5.4%, and 10.7% meals contained 50 muCi [1-14C]-triolein with breath samples collected hourly following the meal, and gluteal fat biopsies obtained at 0 and 24 h. RS, regardless of dose, had no effect on fasting or postprandial insulin, glucose, FFA or TAG concentration, nor on meal fat storage. However, data from indirect calorimetry and oxidation of [1-14C]-triolein to 14CO2 showed that addition of 5.4% RS to the diet significantly increased fat oxidation. In fact, postprandial oxidation of [1-14C]-triolein was 23% greater with the 5.4% RS meal than the 0% meal (p = 0.0062). CONCLUSIONS: These data indicate that replacement of 5.4% of total dietary carbohydrate with RS significantly increased post-prandial lipid oxidation and therefore could decrease fat accumulation in the long-term.     

Impact of overweight and glucose tolerance on postprandial responses to high- and low-glycaemic index meals

The beneficial effects of a low-glycaemic index (GI) meal on postprandial glucose and insulin levels have been demonstrated. However, limited data are available on the impact of overweight and glucose tolerance on postprandial responses to different GI meals. Our aim was to study the effects of physiological characteristics on postprandial glucose, insulin and lipid responses and the relative glycaemic response (RGR) of a low-GI (LGI) and a high-GI (HGI) meal. We recruited twenty-four normal-weight and twenty-four overweight subjects, twelve with normal glucose tolerance (NGT) and twelve with impaired glucose tolerance (IGT) in each group. Both test meals were consumed once and the glucose reference twice. Blood glucose and insulin were measured in the fasting state and over a 2 h period after each study meal, and TAG and NEFA were measured in the fasting state and over a 5 h period. The glucose responses of subjects with IGT differed significantly from those of subjects with NGT. The highest insulin responses to both meals were observed in overweight subjects with IGT. Physiological characteristics did not influence TAG or NEFA responses or the RGR of the meals. The LGI meal resulted in lower glucose (P < 0·001) and insulin (P < 0·001) responses, but higher TAG responses (P < 0·001), compared with the HGI meal. The GI of the meals did not affect the NEFA responses. In conclusion, the LGI meal causes lower glucose and insulin responses, but higher TAG responses, than the HGI meal. The RGR of the meals does not differ between normal-weight and overweight subjects with NGT or IGT.     

Effect of meal sequence on postprandial lipid, glucose and insulin responses in young men

OBJECTIVE: To investigate whether the postprandial changes in plasma triacylglycerol (TAG), nonesterified fatty acids (NEFA), glucose and insulin concentrations in young men were the same if an identical meal was fed at breakfast and lunch, and if the response to lunch was modified by consumption of breakfast. METHODS: In two trials (1 and 2) healthy subjects (age 22+/-1 y, body mass index 22+/-2 kg/m(2)) were fed the same mixed macronutrient meal at breakfast at 08:00 h and lunch at 14:00 h. In the third trial, no breakfast was fed and the overnight fast extended until lunch at 14:00 h. Addition of [1,1,1-(13)C]tripalmitin to one meal in each trial was used to distinguish between endogenous and meal-derived lipids. RESULTS: The postprandial changes in TAG, NEFA and glucose concentrations were similar in trials 1 and 2. The change in plasma total TAG concentration was about two fold less (P<0.05) after lunch compared to breakfast. Postprandial NEFA suppression was the same after breakfast and lunch. Glucose and insulin responses were significantly greater following lunch suggesting decreasing insulin sensitivity during the day. Consumption of breakfast did not alter the postprandial total TAG or NEFA responses after lunch. Measurement of [(13)C]palmitic acid concentration showed that handling of TAG and NEFA from the meal was the same after breakfast and lunch, and was not altered by consumption of breakfast. CONCLUSIONS: Overall, these data suggest that in young, healthy men regulation of plasma TAG from endogenous sources, principally VLDL, but not chylomicrons during the postprandial period leads to differences in the magnitude of lipaemic response when the same meal was consumed at breakfast or at lunch 6 h later.     

The effect of low and moderate fat intakes on the postprandial lipaemic and hormonal responses in healthy volunteers.

Present literature indicates that whereas an acute fat intake of 5 g does not elicit a postprandial triacylglycerolaemic response, 20 g of fat does. Since 67% of fat intake occasions involve fat doses of less than 20 g, the present study examined the effect of a relatively low-fat (LF) meal (0.2 g/kg body weight; mean 14 g) on postprandial triacylglycerol (TAG) metabolism, compared with a high-fat (HF) meal (0.6 g/kg body weight; mean 43 g), a fat dose which is more typical of laboratory studies. Plasma- and chylomicron-TAG concentrations increased significantly (P < or = 0.001) following both meals, and the increase was significantly (P < or = 0.02) greater after the HF meal. The postprandial areas under the curves and maximal postprandial TAG concentrations for plasma- and chylomicron-TAG were significantly higher following the HF meal (P < or = 0.05). Postprandial plasma insulin and gastric inhibitory polypeptide concentrations increased significantly (P < or = 0.001) after each meal, but there was no difference between the two meals. These data show that modest amounts of fat in a meal will elicit a measurable postprandial TAG response. Since postprandial lipaemia affects the composition and concentration of the TAG- and cholesterol-rich lipoproteins, controlling dietary TAG supply may influence the metabolic fate of these lipoproteins.     

Influence of dietary fat on postprandial glucose metabolism (exogenous and endogenous) using intrinsically (13)C-enriched durum wheat.

The present study evaluates the influence of different amounts of fat added to starch on postprandial glucose metabolism (exogenous and endogenous). Nine women (24 (se 2) years old, BMI 20.4 (se 0.7) kg/m(2)) ingested 1 week apart 75 g glucose equivalent of (13)C-labelled starch in the form of pasta without (low fat; LF) or with 15 (medium fat; MF) or 40 (high fat; HF) g sunflower oil. During the 7 h following meal consumption, plasma glucose, non-esterified fatty acids, triacylglycerols (TG) and insulin concentrations, and endogenous (using [6,6-(2)H(2)]glucose) and exogenous glucose turnover were determined. With MF and HF meals, a lower postprandial glucose peak was observed, but with a secondary recovery. A decrease in exogenous glucose appearance explained lower glycaemia in HF. At 4 h after the HF meal the insulin, insulin:glucose and postprandial blood TG were higher than those measured after the LF and MF meals. Despite higher insulinaemia, total glucose disappearance was similar and endogenous glucose production was suppressed less than after the LF and MF meals, suggesting insulin resistance. Thus, the addition of a large amount of fat appears to be unfavourable to glucose metabolism because it leads to a feature of insulin resistance. On the contrary, the MF meal did not have these adverse effects, but it was able to decrease the initial glycaemic peak.     

Gender influence on plasma triacylglycerol response to meals with different monounsaturated and saturated fatty acid content

OBJECTIVE: Both gender and meal fatty acid composition modulate postprandial triacylglycerol (TAG) metabolism, but little information exists on their interaction. We compared postprandial TAG concentrations in men and women after test meals differing in the proportion of monounsaturated (MUFA) and saturated fatty acids (SFA). SUBJECTS: Nine men (body mass index, BMI: 24.5+/-2.3 kg/m(2)) (mean+/-s.d.) and 10 premenopausal women (BMI: 21.2+/-1.7 kg/m(2)), young and healthy, habituated to a relatively high MUFA diet. DESIGN: Plasma responses were studied after subjects consumed two meals, each providing 60 g of fat and 4.7 MJ, on different occasions: one meal was rich in MUFA (MUFA meal: 40 g MUFA; 12 g SFA) and the other meal was rich in SFA (SFA meal: 20 g MUFA; 32 g SFA). The total body and abdominal fat mass were assessed by dual energy X-ray absorptiometry. RESULTS: Fasting plasma TAG concentration did not differ between meals or genders. No gender differences were observed in either total body or abdominal fat mass. The area under the plasma concentration vs time curve was on average 60% higher (P<0.001) in men than women. Repeated measures ANOVA showed a significant effect of meal x time interaction in men (P<0.001) but not in women (P=0.84). In men, maximal plasma TAG occurred at 4 h and was significantly greater after the MUFA meal (2.10+/-0.20 mmol/l) (mean+/-s.e.m.) than after the SFA meal (1.66+/-0.19 mmol/l) (P=0.01). TAG concentration at 5 h was also significantly greater after the MUFA meal. In women, the patterns of TAG responses were identical after the MUFA and SFA meals. CONCLUSIONS: This study provides evidence that gender influences postprandial TAG concentrations when meal fatty acid composition is altered.     

Change in postprandial substrate oxidation after a high-fructose meal is related to body mass index in healthy men

Oral fructose decreases fat oxidation and increases carbohydrate oxidation in obese subjects, but the metabolic response to fructose in lean individuals is less well understood. The purpose of this study was to assess the effects of a single fructose-rich mixed meal on substrate oxidation in young healthy nonobese men. We hypothesized that a decrease in fat oxidation and an increase in carbohydrate oxidation would be observed after a fructose-rich mixed meal compared with a glucose-rich mixed meal. Twelve healthy, normal weight to overweight, aged 23 to 31 years participated in a double-blind, crossover study. Each participant completed 2 study visits, eating a mixed meal containing 30% of the calories from either fructose or glucose. Blood samples for glucose, insulin, triglycerides, and leptin as well as gas exchange by indirect calorimetry were measured intermittently for 7 hours. Serum insulin was higher after a fructose mixed meal, but plasma glucose, plasma leptin, and serum triglycerides were not different. Mean postprandial respiratory quotient and estimated fat oxidation did not differ between the fructose and glucose meals. The change in fat oxidation between the fructose- and glucose-rich meals negatively correlated with body mass index (BMI; r = −0.59 [P = .04] and r = −0.59 [P = .04] at the 4- and 7-hour time points, respectively). In healthy nonobese men, BMI correlates with altered postprandial fat oxidation after a high-fructose mixed meal. The metabolic response to a high-fructose meal may be modulated by BMI.     

PPARgamma, energy balance, and associations with colon and rectal cancer

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been hypothesized as being involved in colorectal cancer given its role in adipocyte development and insulin resistance. In this study we evaluated the association between the Pro12Ala (P12A) PPARgamma polymorphism and body mass index (BMI), waist-to-hip ratio (WHR), physical activity level, and energy intake and risk of colorectal cancer using data from a population-based, case-control study of colon cancer (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls). We further evaluated how the P12A PPARgamma polymorphism is associated with obesity and fat pattern in the control population. The odd ratio for PPARgamma PA or AA genotype relative to the PP genotype for colon cancer was 0.9 (95% confidence interval, CI=0.8-1.0) and for rectal cancer was 1.2 (95% CI=1.0-1.5) adjusting for race, age, and sex. P12A PPARgamma did not significantly interact with BMI, WHR, energy intake, and energy expenditure to alter risk of colon or rectal cancer. Furthermore, the P12A PPARgamma polymorphism was not associated with obesity or WHR in the control population; it did not interact with energy intake or energy expenditure to alter risk of obesity or large WHR. These data do not support the hypothesis that the P12A PPARgamma polymorphism is associated with colon or rectal cancer through regulation of energy balance.     

A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy

Fatty acid transport protein 6 (FATP6) is primarily expressed in the heart and seems to be involved in cardiac fatty acid uptake. Therefore, we investigated whether a variation in the 5'-untranslated region of the FATP6 gene is associated with features of the metabolic syndrome and signs of myocardial alteration or heart failure. A total of 755 male participants from a Metabolic Intervention Cohort Kiel were genotyped for the FATP6-7T>A polymorphism (rs2526246) and phenotyped for features of the metabolic syndrome. Participants underwent a glucose tolerance test and the postprandial assessment of metabolic variables after a standardised mixed meal. Left ventricular heart function was evaluated in fifty-four participants. Fasting (P = 0·01) and postprandial (P = 0·02) TAG concentrations were significantly lower in AA homozygotes when compared with wild-type carriers. Homozygosity of allele A was associated with significantly lower postprandial insulin concentrations after a glucose load and significantly lower systolic (P = 0·01) and diastolic (P = 0·01) blood pressure values compared with wild-type carriers. Accordingly, left ventricular heart mass was significantly lower in twenty-seven AA homozygotes in comparison with twenty-seven TT homozygotes, matched for BMI (P = 0·04). In conclusion, the effects of the FATP6 polymorphism on TAG are mediated by affluent dietary fat. The FATP6-7T>A polymorphism may protect from traits of the metabolic syndrome and CVD.     

Effects of dietary composition on postprandial endothelial function and adiponectin concentrations in healthy humans: a crossover controlled study

BACKGROUND: Abnormalities during the postprandial state contribute to the development of atherosclerosis. Reportedly, postprandial hyperglycemia, hypertriglyceridemia, and hyperlipacidemia independently cause postprandial cytokine activation. However, it is not clear which dietary composition preferentially affects postprandial endothelial function in healthy subjects. OBJECTIVE: We aimed to examine the associations of dietary composition and postprandial endothelial function in healthy subjects. DESIGN: The effects of a single ingestion of a high-carbohydrate meal (300 kcal, 100% carbohydrate), a high-fat meal (30 g fat/m(2), 35% fat), or a standard test meal (478 kcal; 16.4% protein, 32.7% fat, 50.4% carbohydrate) on postprandial plasma concentrations of adiponectin and forearm blood flow (FBF) during reactive hyperemia were studied in healthy subjects. RESULTS: The peak FBF response and the total reactive hyperemic flow (flow debt repayment; FDR), indexes of resistance artery endothelial function, were unchanged after ingestion of a high-carbohydrate and standard test meal but decreased 120 and 240 min after a high-fat meal. After a high-fat meal, decreases in peak FBF and FDR were well correlated with an increase in plasma free fatty acid (FFA) concentrations but not with the other biochemical variables, including triacylglycerol, insulin, glucose, total cholesterol, HDL cholesterol, and adiponectin. CONCLUSIONS: Postprandial endothelial function was impaired only after the high-fat diet and not after the high-carbohydrate or standard test meal in healthy subjects. Because such endothelial dysfunction after a high-fat meal was closely correlated with FFA concentrations, postprandial state could be hazardous, mostly through acute hyperlipacidemia in healthy subjects.     

ACDC/adiponectin and PPAR-gamma gene polymorphisms: implications for features of obesity

OBJECTIVE: The main purpose of this study was to investigate associations of single-nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain-containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator-activated receptor (PPAR)-gamma gene, with body fat mass and its topographical distribution in postmenopausal women. RESEARCH METHODS AND PROCEDURES: Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for four SNPs in the ACDC gene (-11391G/A, -11377C/G, +45T/G, +276G/T) and the Pro12Ala SNP in the PPAR-gamma gene. Total body fat mass and the central to peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin and homeostasis model assessment of insulin resistance were measured in 287 subjects. RESULTS: The -11377C/G SNP was associated with adiponectin (p < 0.001) and the CFM/PFM ratio (p = 0.005); the G allele being associated with low adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p = 0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter haplotype (11391G/A_-11377C/G). Genotype variation of SNP Pro12Ala was associated with total body fat mass (p = 0.04); women with GG being the most obese (p = 0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype of SNP-11377C/G in the determination of BMI (p = 0.001), when analyzed using a codominant model. DISCUSSION: Polymorphisms in the ACDC gene are associated with body fat distribution, whereas the Pro12Ala polymorphism in PPAR-gamma is associated with overall adiposity, apparently in interaction with an ACDC promoter SNP.     

The association between plasma adiponectin and insulin sensitivity in humans depends on obesity

OBJECTIVE: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. RESEARCH METHODS AND PROCEDURES: We investigated the cross-sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose-tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. RESULTS: In cross-sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin x PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R2 = 0.10, p = 0.13, OGTT; and R2 = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R2 = 0.36, p < 0.0001, OGTT; and R2 = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. DISCUSSION: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin-resistant individuals.