Sam Amir H, Sleeth Michelle L, Thomas E Louise, Ismail Nurhafzan A, Mat Daud Norlida, Chambers Edward, Shojaee-Moradie Fariba, Umpleby Margot, Goldstone Anthony P, Le Roux Carel W, Bech Paul, Busbridge Mark, Laurie Rosemary, Cuthbertson Daniel J, Buckley Adam, Ghatei Mohammad A, Bloom Stephen R, Frost Gary S, Bell Jimmy D, Murphy Kevin G
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (A.S., C.W.L.R., P.B., R.L., A.B., M.A.G., S.R.B., K.G.M.), Imperial College London, United Kingdom; Nutrition and Dietetic Research Group, Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (M.L.S., N.A.I., N.M.D., E.C., G.S.F.), Imperial College London, United Kingdom; Department of Life Sciences, Faculty of Science and Technology (E.L.S., J.D.B.), University of Westminster, London, United Kingdom; School of Chemical Sciences and Food Technology, Faculty of Science and Technology (N.M.D.), Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia; Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences (F.S.M., M.U.), University of Surrey, Guildford, United Kingdom; Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (A.P.G.), Imperial College London, United Kingdom; Diabetes Complications Research Centre (C.W.L.R.), Conway Institute, University College Dublin, Ireland; Department of Clinical Biochemistry (P.B., M.B.), Imperial College Healthcare NHS Trust, London, United Kingdom; and Department of Obesity and Endocrinology (D.J.C.), Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom.
J Clin Endocrinol Metab. 2015 Mar;100(3):1048-52. doi: 10.1210/jc.2014-3450. Epub 2014 Dec 9.
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.
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.
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).
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.
目前尚无生物标志物能够可靠地预测内脏脂肪和肝脏脂肪含量，而这两者均为心血管疾病的危险因素。有研究表明迷走神经张力会影响局部脂肪沉积。胰腺多肽（PP）由内分泌胰腺在迷走神经控制下分泌。我们研究了PP在预测内脏脂肪和肝脏脂肪方面的效用。
对104名超重和肥胖受试者（46名男性和58名女性）测量空腹血浆PP浓度。在同一批受试者中，使用全身磁共振成像测量总脂肪组织和局部脂肪组织，包括总内脏脂肪组织（VAT）和总皮下脂肪组织（TSAT）。通过质子磁共振波谱法定量测定肝细胞内脂质含量（IHCL）。
空腹血浆PP浓度与VAT（r = 0.57，P <.001）和IHCL（r = 0.51，P <.001）均呈显著正相关，但与TSAT无相关性（r = 0.02，P =.88）。在控制年龄和性别后，空腹PP浓度可独立预测VAT。在控制年龄、性别、体重指数（BMI）、腰臀比、稳态模型评估2-胰岛素抵抗（HOMA2-IR）以及甘油三酯（TG）、总胆固醇（TC）和丙氨酸转氨酶（ALT）的血清浓度后，空腹PP浓度可独立预测IHCL。空腹PP浓度与血清ALT、TG、TC、低密度和高密度脂蛋白胆固醇以及血压相关（P <.05）。这些关联由IHCL和/或VAT介导。空腹PP和HOMA2-IR与肝脂肪变性独立显著相关（P <.01）。
胰腺多肽是内脏脂肪和肝脏脂肪含量的新型预测指标，因此是心血管风险分层及异位脂肪沉积患者靶向治疗的潜在生物标志物。
