Abstract
Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disorder, but the factors that determine this heterogeneity remain poorly understood. Adipose tissue (AT) dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance (IR) and pro-inflammatory adipokines release. While many studies in NAFLD have looked at total adiposity (that is mainly subcutaneous fat, SC-AT), it is still unclear the impact of visceral fat (VF). Thus, we investigated how VF vs. SC-AT were related to NAFLD in lean, overweight, and obese individuals compared to lean controls.
Methods Thirty-four non-diabetic NAFLD with liver biopsy and eight lean control individuals (CT) were enrolled in this study. We measured fat distribution (VF, SC-AT and IHTG) by magnetic resonance imaging (MRI), adiponectin concentration, free fatty acids (FFAs) and triglyceride (TAG) concentration and composition by mass spectrometry (MS), lipolysis and IR by tracer infusion.
Results IHTG was positively associated with lipolysis, adipose tissue IR, TG concentrations, and increased ratio of saturated/unsaturated fatty acids. VF was higher in NAFLD (including lean individuals) compared to controls, was increased with fibrosis stage and was associated with IR in liver, muscle and adipose tissue, increased lipolysis, and decreased adiponectin levels. Collectively, our results suggest that VF accumulation, given its location close to the liver, is one of the major risk factors for NAFLD.
Conclusions These findings propose VF as an early indicator of NAFLD independently of BMI, which may allow for evidence-based prevention and intervention strategies.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of Interest statement/Financial Disclosure The authors declare no conflict of interest for this manuscript.
Abbreviations
- NAFLD
- Nonalcoholic fatty liver disease
- AT
- Adipose tissue
- IHTG
- Intrahepatic triglyceride
- IR
- Insulin resistance
- SC-AT
- Subcutaneous fat
- VF
- Visceral fat
- FFAs
- Free fatty acids
- TAG
- Triglyceride
- MS
- Mass spectrometry
- NASH
- Non-alcoholic steatohepatitis
- MRI
- Magnetic resonance imaging
- HDL
- High density lipoprotein
- LDL
- Low density lipoprotein
- LFTs
- Liver function tests
- APO-B
- Apolipoprotein B
- APO-A1
- Apolipoprotein A1
- NAS
- NAFLD activity score
- ROI
- Region of interest
- LFF
- Liver fat fraction
- EGP
- Endogenous glucose production
- Hep-IR
- Hepatic insulin-resistance
- Muscle-IR
- Muscle insulin-resistance
- Adipo-IR and Lipo-IR
- Adipose tissue insulin-resistance
- ALT
- Alanine aminotransferase
- AST
- Aspartate aminotransferase
- GGT
- Gamma-glutamyltransferase