OBJECTIVE-Atrial natriuretic peptide (ANP) regulates arterial blood pressure. In addition, ANP has recently been shown to promote human adipose tissue lipolysis through cGMPmediated hormone-sensitive lipase activation. We hypothesized that ANP increases postprandial free fatty acid (FFA) availability and energy expenditure while decreasing arterial blood pressure. RESEARCH DESIGN AND METHODS-We infused human ANP (25 ng ⅐ kgϪ1 ⅐ min Ϫ1 ) in 12 men (age 32 Ϯ 0.8 years, BMI 23.3 Ϯ 0.4 kg/m 2 ) before, during, and 2 h after ingestion of a standardized high-fat test meal in a randomized, double-blind, cross-over fashion. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. Metabolism was monitored through venous blood sampling, intramuscular and subcutaneous abdominal adipose tissue microdialysis, and indirect calorimetry.RESULTS-ANP infusion decreased mean arterial blood pressure by 4 mmHg during the postprandial phase (P Ͻ 0.01 vs. placebo). At the same time, ANP induced lipolysis systemically (P Ͻ 0.05 vs. placebo) and locally in subcutaneous abdominal adipose tissue (P Ͻ 0.0001 vs. placebo), leading to a 50% increase in venous glycerol (P Ͻ 0.01) and FFA (P Ͻ 0.05) concentrations compared with placebo. The increase in FFA availability with ANP was paralleled by a 15% increase in lipid oxidation rates (P Ͻ 0.05 vs. placebo), driving a substantial increase in postprandial energy expenditure (P Ͻ 0.05 vs. placebo). A modest mismatch between energy intake and expenditure elicits major changes in body weight over years. Total daily energy expenditure comprises resting metabolic rate, physical activity, and postprandial thermogenesis. Measures that increase postprandial thermogenesis could prevent or treat obesity. Pharmacological strategies to augment energy expenditure have been unsuccessful because of side effects (1). Manipulation of adrenergic transmission is associated with increased thermogenesis, blood pressure elevations, and other cardiac side effects (2). Atrial natriuretic peptide (ANP) has recently been shown to promote adipose tissue lipolysis through cGMP-mediated, hormone-sensitive lipase activation (3). ANP-mediated lipolysis has only been observed in primates such as macaques and humans but not in other species (4). ANP increases circulating free fatty acid (FFA) levels in human subjects (5-8). Previous studies with adrenergic agonists suggested that increased circulating FFA concentrations can drive an increase in energy expenditure (9). In our earlier studies, ANP-mediated lipolysis did not alter energy expenditure in the fasted state, whereas lipid oxidation rate increased slightly (6,8). We now tested the hypothesis that ANP augments postprandial FFA availability, lipid oxidation, and energy expenditure while concomitantly decreasing blood pressure in healthy young men. CONCLUSIONS-Our RESEARCH DESIGN AND METHODSWe recruited 12 healthy, nonoverweight, nonobese individuals aged 32 Ϯ 0.8 years with BMI 23.3 Ϯ 0.4 kg/m 2 . Subjects did not ...

Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

OBJECTIVELow cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL.RESEARCH DESIGN AND METHODSWe included 138 overweight to obese, otherwise healthy subjects (aged 43.6 ± 8.9 years, BMI 33.8 ± 4 kg/m2). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individual's CRF. Insulin sensitivity was determined during an oral glucose tolerance test.RESULTSFor all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = −0.27, P < 0.05), and visceral (r = −0.25, P < 0.05) and total fat mass (r = −0.32, P < 0.05), but not to intramyocellular lipids (r = −0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r2 = −0.43, P < 0.01, r2 = −0.34, and r2 = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels.CONCLUSIONSOur study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction.

Endurance training at an intensity eliciting maximal fat oxidation may have a beneficial effect on body weight and glucose metabolism in obese patients. However, the exercise intensity at which maximal fat oxidation occurs and the factors limiting fat oxidation are not well studied in this population. Obese, otherwise healthy men (n=38) and women (n=91) performed an incremental exercise test up to exhaustion on a cycle ergometer. Substrate oxidation was estimated using indirect calorimetry. Magnetic resonance tomography and spectroscopy were conducted to assess body fat distribution and intramyocellular fat content. We determined the exercise intensity at which maximal body fat oxidation occurs and assessed whether body composition, body fat distribution, intramyocellular fat content, or oxidative capacity predict exercise-induced fat oxidation. Maximal exercise-induced fat oxidation was 0.30+/-0.02 g/min in men and 0.23+/-0.01 g/min in women (p<0.05). Exercise intensity at the maximum fat oxidation was 42+/-2.2% VO (2 max) in men and 43+/-1.7% VO (2 max) in women. With multivariate analysis, exercise-induced fat oxidation was related to fat-free mass, percent fat mass, and oxidative capacity, but not to absolute fat mass, visceral fat, or intramyocellular fat content. We conclude that in obese subjects the capacity to oxidize fat during exercise appears to be limited by skeletal muscle mass and oxidative capacity rather than the availability of visceral or intramyocellular fat.