Human and molecular genetics shed lights on fatty liver disease and diabetes conundrum

Federica Tavaglione, Giovanni Targher, Luca Valenti, Stefano Romeo

Research output: Contribution to journalReview articlepeer-review

Abstract

The causal role of abdominal overweight/obesity, insulin resistance and type 2 diabetes (T2D) on the risk of fatty liver disease (FLD) has robustly been proven. A consensus of experts has recently proposed the novel definition of ‘metabolic dysfunction-associated fatty liver disease, MAFLD’ instead of ‘nonalcoholic fatty liver disease, NAFLD’, emphasizing the central role of dysmetabolism in the disease pathogenesis. Conversely, a direct and independent contribution of FLD per se on risk of developing T2D is still a controversial topic. When dealing with FLD as a potential risk factor for T2D, it is straightforward to think of hepatic insulin resistance as the most relevant underlying mechanism. Emerging evidence supports genetic determinants of FLD (eg PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B13) as determinants of insulin resistance and T2D. However, recent studies highlighted that the key molecular mechanism of dysmetabolism is not fat accumulation per se but the degree of hepatic fibrosis (excess liver fat content—lipotoxicity), leading to reduced insulin clearance, insulin resistance and T2D. A consequence of these findings is that drugs that will ameliorate liver fat accumulation and fibrosis in principle may also exert a beneficial effect on insulin resistance and risk of T2D in individuals with FLD. Finally, initial findings show that these genetic factors might be directly implicated in modulating pancreatic beta-cell function, although future studies are needed to fully understand this relationship.

Original languageEnglish
Article numbere00179
JournalEndocrinology, Diabetes and Metabolism
Volume3
Issue number4
DOIs
Publication statusPublished - 2020

Keywords

  • diabetes
  • fatty liver disease
  • human genetics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Human and molecular genetics shed lights on fatty liver disease and diabetes conundrum'. Together they form a unique fingerprint.

Cite this