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Machado. Hepatoma Res 2020;6:84 Hepatoma Research
DOI: 10.20517/2394-5079.2020.90

Review Open Access

Nonalcoholic fatty liver disease in lean subjects:
is it all metabolic-associated fatty liver disease?

Mariana Verdelho Machado 1,2

1 Faculdade de Medicina, Universidade de Lisboa, Lisbon 1649-035, Portugal.
2 Gastroenterology Department, Hospital de Vila Franca de Xira, Lisbon 1649-035, Portugal.
Correspondence to: Prof. Mariana Verdelho Machado, Gastroenterology Department, Faculdade de Medicina, Universidade de
Lisboa, Avenida Professor Egas Moniz, Lisbon 1649-035, Portugal. E-mail: mverdelhomachado@gmail.com
How to cite this article: Machado MV. Nonalcoholic fatty liver disease in lean subjects: is it all metabolic-associated fatty liver
disease? Hepatoma Res 2020;6:84. http://dx.doi.org/10.20517/2394-5079.2020.90
Received: 25 Aug 2020 First Decision: 29 Sep 2020 Revised: 25 Oct 2020 Accepted: 5 Nov 2020 Published: 5 Dec 2020

Academic Editor: Stefano Bellentani Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
The epidemiology of nonalcoholic fatty liver disease goes hand-in-hand with the obesity pandemic. The
Received: First Decision: Revised: Accepted: Published:
pathogenesis of fatty liver has shifted from an hepatocentric view to an adipocentric view, in which the overloaded
Science Editor: Copy Editor: Production Editor: Jing Yu adipose tissue spills out lipids that spread to ectopic tissues and organs such as the liver, elicits inflammation,
and changes its adipokines profile promoting insulin resistance and the metabolic syndrome. Up to 40% of
nonalcoholic fatty liver disease (NAFLD) patients are not obese and up to 20% are actually lean. Furthermore
roughly 10% of lean subjects have NAFLD. In fact, adiposopathy can occur in patients with normal weight, and
it is associated with expansion of metabolically active visceral fat and a qualitatively different adipose tissue
that becomes overwhelmed after challenged by a mildly positive energy balance. This defines the concept of
personal fat threshold that when exceeded results in metabolic dysfunction. Overweight/obese persons have
higher probability of exceeding that threshold, explaining why adiposopathy/metabolic syndrome/NAFLD is
more frequent in the obese. In this article, the epidemiology, pathogenesis, and management of patients with lean
NAFLD are reviewed with an emphasis on reconciling the concepts of NAFLD in its relationship with adiposity and
of NAFLD in lean individuals.

Keywords: Lean nonalcoholic fatty liver disease, metabolically obese normal weight, visceral adipose tissue

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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