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

Yftach Gepner, Ilan Shelef, Oded Komy, Noa Cohen, Dan Schwarzfuchs, Nitzan Bril, Michal Rein, Dana Serfaty, Shira Kenigsbuch, Hila Zelicha, Anat Yaskolka Meir, Lilac Tene, Avital Bilitzky, Gal Tsaban, Yoash Chassidim, Benjamin Sarusy, Uta Ceglarek, Joachim Thiery, Michael Stumvoll, Matthias BlüherMeir J. Stampfer, Assaf Rudich, Iris Shai

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


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.

Original languageEnglish
Pages (from-to)379-388
Number of pages10
JournalJournal of Hepatology
Issue number2
StatePublished - 1 Aug 2019


  • Cardiovascular risk
  • Clinical trial
  • Diet
  • Hepatic fat content
  • Lifestyle
  • Low carbohydrate
  • Visceral adipose tissue

ASJC Scopus subject areas

  • Hepatology


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