The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content

J Hepatol. 2019 Aug;71(2):379-388. doi: 10.1016/j.jhep.2019.04.013. Epub 2019 May 8.


Background & aim: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes.

Methods: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months.

Results: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes.

Conclusions: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss.

Lay summary: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. Identifier: NCT01530724.

Keywords: Cardiovascular risk; Clinical trial; Diet; Hepatic fat content; Lifestyle; Low carbohydrate; NAFLD; Visceral adipose tissue.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Diet, Fat-Restricted*
  • Diet, Mediterranean*
  • Dyslipidemias / diagnostic imaging
  • Dyslipidemias / diet therapy*
  • Exercise
  • Fatty Liver / diagnostic imaging
  • Fatty Liver / diet therapy*
  • Female
  • Humans
  • Intra-Abdominal Fat
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Obesity, Abdominal / diagnostic imaging
  • Obesity, Abdominal / diet therapy*
  • Treatment Outcome
  • Weight Loss

Associated data