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Context and objective: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat. Patients and Methods: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy. Results: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01). Conclusions: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.

Nonalcoholic fatty liver disease may be evident in women with polycystic ovary syndrome (PCOS), both conditions being associated with obesity and insulin resistance. However, few studies have accounted for the high prevalence of obesity in PCOS.The aim of this study was to determine whether PCOS is independently associated with hepatic steatosis, compared with healthy controls of similar age and body mass index (BMI), and whether steatosis is associated with hyperandrogenemia.We conducted a cross-sectional, case-control study at two tertiary referral centers.Twenty-nine women with PCOS diagnosed by the Rotterdam criteria [aged 28 yr; 95% confidence interval (CI), 26-31; BMI, 33 kg/m2; 95% CI, 31-36] and 22 healthy controls (aged 29 yr; 95% CI, 28-31; BMI, 30 kg/m2; 95% CI, 28-33) were studied.Proton-magnetic resonance spectroscopy quantified hepatic and skeletal muscle fat; whole body magnetic resonance imaging quantified internal, visceral, and sc adipose tissue volumes. Differences were assessed between PCOS and controls using t tests, and between hyperandrogenic (HA) PCOS, PCOS with normal androgens (NA), and controls using analysis of covariance.After statistical adjustment for BMI, HA-PCOS had significantly higher liver fat vs. NA-PCOS (3.7%; 95% CI, 0.6-13.1) and vs. controls (2.1%; 95% CI, 0.3-6.6). Similarly, after adjustment for homeostasis model assessment for insulin resistance, internal and visceral adipose tissue volumes, liver fat remained significantly greater in HA-PCOS compared to NA-PCOS and controls.These data suggest that HA-PCOS is associated with hepatic steatosis, independent of obesity and insulin resistance.

Context: High plasma triglycerides (TG) have been shown to be independent and better predictors of cardiovascular disease than low-density lipoprotein (LDL) cholesterol in women. This may be due to gender differences in very-low-density lipoprotein 1 (VLDL1)- and VLDL2-TG and fatty acid kinetics. Objective: Our objective was to investigate whether there are differences in VLDL1- and VLDL2-TG and fatty acid kinetics in obese men and postmenopausal women, a high risk group for cardiovascular disease. Research Design and Methods: Stable isotopes techniques were used to measure fasting palmitate rate of appearance, metabolic clearance rate, oxidation rate, and nonoxidative disposal rate, VLDL1-TG and VLDL2-TG fractional catabolic rate (FCR) and production rate (PR). Whole-body fat distribution was measured by magnetic resonance imaging. Participants: Participants included 10 postmenopausal obese women and eight obese men matched for age, body mass index, and fasting plasma TG. Results: The women had lower visceral fat and higher sc fat than the men (P lt 0.001 and P lt 0.002). Palmitate rate of appearance, metabolic clearance rate, nonoxidative disposal rate, and oxidation rate corrected for resting energy expenditure were greater in the women than the men (all P lt 0.03). VLDL2-TG PR corrected for fat-free mass was higher in the women (P lt 0.001). VLDL2-TG and VLDL2-cholesterol pools were higher in the women (P lt 0.001 and P lt 0.008). VLDL1-TG FCR and PR and VLDL2-TG FCR were not different between genders. Conclusion: Fatty acid and VLDL2-TG flux is higher in postmenopausal obese women than in obese men matched for fasting plasma TG levels. (J Clin Endocrinol Metab 97: 2475-2481, 2012)

Visceral obesity is detrimental to health, but the mechanisms controlling body fat distribution are not fully understood. In premenopausal adult females (30 nonobese, 14 obese [body mass index> 30kg/m2]), variance in fasting insulin, glucose, insulin/glucose ratio, C-peptide/insulin ratio, triglycerides, and high-density lipoprotein/low-density lipoprotein-cholesterol ratio, were independently influenced by visceral but not total sc or abdominal sc adipose tissue, as measured by whole-body magnetic resonance imaging. Adult females with Prader-Willi syndrome (n = 13) had significantly reduced visceral adiposity, compared with obese controls (visceral/total sc adipose tissue ratio: 0.067 ± 0.017 vs. 0.108 ± 0.021), independent of their total adiposity (P < 0.001), or use of exogenous sex steroids. This is in contrast to that expected by their physical inactivity, hypogonadism, adult GH deficiency, and psychiatric problems. Females with Prader-Willi syndrome not receiving sex steroids (n = 8) had significantly reduced fasting insulin, insulin/glucose ratio, and triglycerides and increased C-peptide/insulin ratio, compared with obese controls, adjusting for total (P < 0.05) but not visceral adiposity (P = 0.3–0.6), supporting their association. The cause of the reduced visceral adiposity in Prader-Willi syndrome may reflect novel hormonal, hypothalamic, and/or genetic influences on body fat distribution.