Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease

Abstract

Background & aims: Steatosis in patients with nonalcoholic fatty liver disease (NAFLD) is due to an imbalance between intrahepatic triglyceride (IHTG) production and export. The purpose of this study was to evaluate TG metabolism in adipose tissue and liver in NAFLD.

Methods: Fatty acid, VLDL-TG, and VLDL-apolipoprotein B-100 (apoB100) kinetics were assessed by using stable isotope tracers in 14 nondiabetic obese subjects with NAFLD (IHTG, 22.7% +/- 2.0%) and 14 nondiabetic obese subjects with normal IHTG content (IHTG, 3.4% +/- 0.4%), matched on age, sex, body mass index, and percent body fat.

Results: Compared with the normal IHTG group, the NAFLD group had greater rates of palmitate release from adipose tissue into plasma (85.4 +/- 6.6 and 114.1 +/- 8.1 micromol/min, respectively; P = .01) and VLDL-TG secretion (11.4 +/- 1.1 and 24.3 +/- 3.1 micromol/min, respectively; P = .001); VLDL-apoB100 secretion rates were not different between groups. The increase in VLDL-TG secretion was primarily due to an increased contribution from "nonsystemic" fatty acids, presumably derived from lipolysis of intrahepatic and intra-abdominal fat and de novo lipogenesis. VLDL-TG secretion rate increased linearly with increasing IHTG content in subjects with normal IHTG but reached a plateau when IHTG content was >/=10% (r = 0.618, P < .001).

Conclusions: Obese persons with NAFLD have marked alterations in both adipose tissue (increased lipolytic rates) and hepatic (increased VLDL-TG secretion) TG metabolism. Fatty acids derived from nonsystemic sources are responsible for the increase in VLDL-TG secretion. However, the increase in hepatic TG export is not adequate to normalize IHTG content.

Figure 1

Whole-body palmitate rate of appearance (Ra) in plasma in subjects with normal intrahepatic triglyceride (IHTG) content and increased IHTG content (nonalcoholic fatty liver disease [NAFLD]). *Value significantly different from the Normal IHTG group value, P < .05.

Figure 2

(A) Total VLDL-TG secretion rate (sum of shaded and open bars) in subjects with normal and increased (nonalcoholic fatty liver disease [NAFLD]) intrahepatic triglyceride (IHTG) content. Open bars represent fatty acids in VLDL-TG that originated from systemic plasma free fatty acids, presumably derived primarily from lipolysis of subcutaneous fat, whereas shaded bars represent fatty acids in VLDL-TG that originated from nonsystemic fatty acids, presumably derived primarily from lipolysis of intrahepatic and visceral fat and de novo lipogenesis. *Value significantly different from corresponding value in the normal IHTG group, P <.05. (B) VLDL-apoB100 secretion rates in the subjects with normal IHTG content (open bar) and NAFLD (solid bar). Values for each group are not significantly different from each other. (C) Molar ratio of VLDL-TG and VLDL-apoB100 secretion rates, an index of the average TG content of nascent VLDL particles, in subjects with normal IHTG content (open bar) and NAFLD (solid bar). *Value significantly different from value in the normal IHTG group, P < .01.

Figure 3

Relationship between VLDL-TG secretion rate and intrahepatic triglyceride content (IHTG) in subjects with normal IHTG (open boxes) and nonalcoholic fatty liver disease (NAFLD) (solid boxes).