Relationship between circulating Fatty Acid Binding Protein-4 (FABP4), subcutaneous and visceral adiposity, and insulin sensitivity in overweight and obese humans. — ASN Events
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  3. Relationship between circulating Fatty Acid Binding Protein-4 (FABP4), subcutaneous and visceral adiposity, and insulin sensitivity in overweight and obese humans.

Relationship between circulating Fatty Acid Binding Protein-4 (FABP4), subcutaneous and visceral adiposity, and insulin sensitivity in overweight and obese humans. (#132)

Katherine T Tonks 1 2 , James Cantley 2 , Aimin Xu 3 , Dorit Samocha-Bonet 2 4 , Don J Chisholm 1 5 , David E James 2 4 , Jerry R Greenfield 1 2 4
  1. Department of Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia
  2. Diabetes & Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
  3. Department of Medicine and Pharmacology, University of Hong Kong, Hong Kong, China
  4. Department of Medicine, University of New South Wales, Sydney, NSW, Australia
  5. Diabetes & Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia

Introduction: Fatty Acid Binding Protein-4 (FABP4) is an adipocyte-derived lipid binding protein. The relative contribution of different adipose depots to circulating FABP4 levels in obese individuals with varying insulin resistance or type 2 diabetes (T2D) has not been investigated.

Aim: To determine the effects of adiposity on circulating FABP4 levels in individuals with varying degrees of insulin resistance or T2D.

Methods: Subjects were 23 lean (BMI≤25kg/m2, HOMA-IR 1.1±0.4), 21 overweight/obese insulin-resistant (Obresistant, BMI>25kg/m2, HOMA-IR 4.3±1.0), 21 T2D (BMI>25kg/m2), and 16 overweight/obese insulin-sensitive (Obsensitive, BMI<25kg/m2, HOMA-IR 1.1±0.4) individuals. Study procedures included OGTT (except T2D), hyperinsulinaemic (80mU/m2/min)-euglycaemic (5mmol/L) clamp, fat determination by CT and DEXA scan, and baseline and clamp steady state measurement of FABP4 by sandwich enzyme-linked immunosorbent assays.

Results: Compared to lean subjects, FABP4 was significantly higher in Obresistant, T2D and Obsensitive individuals at baseline and clamp steady state (2-way ANOVA p=<0.001, 0.037 and 0.024, respectively). The overweight/obese groups (Obresistant, T2D and Obsensitive) had similar FABP4 levels at baseline and steady state. Baseline FABP4 correlated positively with total, central abdominal, visceral and subcutaneous fat (all p≤0.001), but not liver fat (p=0.13). Baseline FABP4 correlated with clamp-derived glucose infusion rate (GIR/FFM) in overweight/obese non-diabetic individuals (r=0.39, p=0.019), yet not when subjects with T2D were included. In a multilinear regression in non-diabetic subjects, inclusive of visceral, subcutaneous and liver fat, GIR/FFM, and OGTT-derived insulin secretion, only subcutaneous fat, GIR/FFM and visceral fat were retained. These explained 55% of the variance in baseline FABP4 (p<0.001), with 43% of FABP4 variation attributable to subcutaneous fat.

Conclusions: FABP4 is predominantly related to subcutaneous adipose tissue volume in humans. Higher FABP4 predicted greater insulin sensitivity in non-diabetic overweight/obese subjects. The uncoupling of GIR from FABP4 in T2D suggests failure of FABP4 action may underlie progression to T2D in obesity.