The blunted effect of glucose-dependent insulinotropic polypeptide in subcutaneous abdominal adipose tissue in obese subjects is partly reversed by weight loss.

P Nordby,M Asmar,L Simonsen,J Bülow,N Arngrim,J J Holst,A Asmar

doi:10.1038/nutd.2016.15

Abstract

Background:Glucose-dependent insulinotropic polypeptide (GIP) appears to have impaired effect on subcutaneous abdominal adipose tissue metabolism in obese subjects. The aim of the present study was to examine whether weight loss may reverse the impaired effect of GIP on subcutaneous abdominal adipose tissue in obese subjects.Methods:Five obese males participated in a 12-week weight loss program, which consisted of caloric restriction (800 Cal day−1) followed by 4 weeks of weight-maintenance diet. Before and after weight loss, subcutaneous adipose tissue lipid metabolism was studied by conducting regional measurements of arterio-venous plasma concentrations of metabolites and blood flow (adipose tissue blood flow, ATBF) across a segment of the abdominal adipose tissue in the fasting state and during GIP infusion (1.5 pmol kg−1 min−1) in combination with a hyperinsulinemic–hyperglycemic clamp.Results:After weight loss (7.5±0.8 kg), glucose tolerance and insulin sensitivity increased significantly as expected. No significant differences were seen in basal ATBF before (1.3±0.4 ml min−1 100 g tissue−1) and after weight loss (2.1±0.4 ml min−1 100 g tissue)−1; however, a tendency to increase was seen. After weight loss, GIP infusion increased ATBF significantly (3.2±0.1 ml min−1 100 g tissue−1) whereas there was no increase before weight loss. Triacylglycerol (TAG) uptake did not change after weight loss. Baseline free fatty acid (FFA) and glycerol output increased significantly after weight loss, P<0.001. During the clamp period, FFA and glycerol output declined significantly, P<0.05, with no differences before and after weight loss. Weight loss increased glucose uptake and decreased FFA/glycerol ratio during the clamp period, P<0.05.Conclusions:In obese subjects, weight loss, induced by calorie restriction, improves the blunted effect of GIP on subcutaneous abdominal adipose tissue metabolism.

Highlights

In healthy normal-weight subjects, subcutaneous abdominal adipose tissue blood flow (ATBF) increases from two- to threefold in response to nutritional stimuli,[1,2] suggesting that a link may exist between the gastrointestinal tract and ATBF
A novel finding in the present study is that weight loss induced by caloric restriction partly restored the increase in ATBF during Glucose-dependent insulinotropic polypeptide (GIP)
With the increase in ATBF, mass reduction might have a role in the diet-induced effect on an increase in glucose uptake and free fatty acid (FFA) re-esterification took place while the glycerol output was reduced to similar levels before and after weight

Summary

Introduction

In healthy normal-weight subjects, subcutaneous abdominal adipose tissue blood flow (ATBF) increases from two- to threefold in response to nutritional stimuli,[1,2] suggesting that a link may exist between the gastrointestinal tract and ATBF. We showed that the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may regulate ATBF.[3] GIP in combination with a hyperinsulinemic–hyperglycemic clamp — with plasma glucose and insulin concentrations similar to those found after ingestion of a carbohydrate-rich meal — increased ATBF, resulting in an increase in triglyceride (TAG) deposition in the subcutaneous abdominal adipose tissue.[3] These effects seem to be beneficial, as efficient fat deposition in the subcutaneous adipose depots protects other tissues from potentially hazardous, prolonged exposure to high levels of lipids postprandially Both fasting ATBF and its responsiveness to nutrients are reduced in obese individuals.[4]. CONCLUSIONS: In obese subjects, weight loss, induced by calorie restriction, improves the blunted effect of GIP on subcutaneous abdominal adipose tissue metabolism

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