Bile Acids More Closely Align with Insulin Resistance and Visceral and Hepatic Adiposity Than Total Body Fat in Adult Humans

Presentation Number: MON 588
Date of Presentation: April 3rd, 2017

Ramy H Bishay*1, Katherine Thuy Trang Tonks2, Jacob George3, Dorit Samocha-Bonet2, Donald John Chisholm2, David E James4 and Jerry R Greenfield5
1St Vincent's Hospital, Sydney, Australia, 2Garvan Institute of Medical Research, Sydney, Australia, 3Westmead Millennium Institute, Sydney, Australia, 4Sydney Medical School, Camperdown, Australia, 5Garvan Institute of Medical Research, Darlinghurst, Australia

Abstract

INTRODUCTION Bile acids (BA) are complex signalling molecules that, in addition to their classical roles as hepatobiliary facilitators of metabolite excretion and absorption of lipophilic nutrients, have a potential role in insulin resistance and obesity, though the exact mechanism remains elusive. We hypothesised that BA concentration is increased in obesity and/or insulin resistance. METHODS Seventy-one adult volunteers formed four groups based on BMI, homeostatic model assessment of insulin resistance (HOMA-IR) and a 75-g OGTT: lean insulin-sensitive (BMI≤25 kg/m2, HOMA-IR<2.0, n=19), overweight/obese insulin-sensitive non-diabetic (Obsen, BMI>25 kg/m2, HOMA-IR<1.5, n=11), overweight/obese insulin-resistant (Obres, BMI>25 kg/m2, HOMA-IR>3.0, n=20) and type 2 diabetes mellitus (T2DM, n=21). We measured insulin sensitivity (glucose disposal rate [GDR]/fat-free mass [FFM]) by hyperinsulinaemic-euglycaemic clamp, body composition/central abdominal fat by dual energy X-ray absorptiometry, visceral fat area by computed tomography and fasting insulin, adiponectin and BA. RESULTS In group comparisons, GDR/FFM was significantly lower, and visceral and liver fat significantly higher, in Obres compared to lean and Obsen subjects, despite similar total adiposity in Obres and Obsen (data not shown). Total BA concentration was higher in Obres (1.35 ± 1.1 mmol/L, P=0.04) and in T2DM (1.26 ± 0.85 mmol/L, P=0.0004) versus Obsen (0.67 ± 0.28 mmol/L), but were similar between Obsen and lean (1.00 ± 0.69 mmol/L). The primary (cholic acid, CA; chenodeoxycholic, CDCA) and secondary (deoxycholic acid, DA) bile acids were significantly associated with waist circumference (CA, R=0.34, P=0.003; CDCA, R=0.26, P=0.03; DA, R=0.37, P=0.001) and central abdominal fat (% or kg) (CA, R=0.28, P=0.01; CDCA, R=0.24, P=0.04; DA, R=0.29, P=0.01). Only CA was associated with BMI (R=0.25, P=0.03), visceral fat (R=0.24, P=0.04) and liver density (an inverse marker of hepatic fat, r=-0.26, p=0.03). In addition, DA was negatively associated with GDR/FFM (R=-0.43, P=0.0002) and adiponectin levels (R=-0.34, P=0.004). CONCLUSION Our data suggest that BA concentrations correlated with insulin resistance and its markers, including central abdominal, visceral and liver fat in humans. Whether BA play an aetiolgoical role in insulin resistance is yet to be elucidated.

 

Nothing to Disclose: RHB, KTTT, JG, DS, DJC, DEJ, JRG