Polyphenols and non-alcoholic fatty liver disease: impact and mechanisms

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of the metabolic syndrome and its prevalence is rapidly increasing due to its strong association with insulin resistance and obesity. At present, given that NAFLD is highly prevalent and therapies are limited, much attention is focused on identifying effective dietary strategies for the prevention and treatment of the disease. Polyphenols are a group of plant bioactive compounds whose regular consumption have been associated with a reduction in the risk of a number of metabolic disorders associated with NAFLD. Here we review the emerging and relatively consistent evidence from cell culture and rodent studies showing that select polyphenols positively modulate a variety of contributors to the NAFLD phenotype, through diverse and complementary mechanisms of action. In particular, the reduction of de novo lipogenesis (via sterol regulatory element-binding protein 1c) and increased fatty acid β-oxidation, presumably involving AMP-activated protein kinase activation, will be discussed. The indirect antioxidant and anti-inflammatory properties of polyphenols which have been reported to contribute to the amelioration of NAFLD will also be addressed. In addition to a direct study of the liver, rodent studies have provided insight into the impact of polyphenols on adipose tissue function and whole body insulin sensitivity, which are likely to in part modulate their impact on NAFLD development. Finally an overview of the limited data from clinical trials will be given along with a discussion of the dose extrapolation from animal studies to human subjects.

Polyphenols treatment in patients with nonalcoholic fatty liver disease

“…[19,20] Fruits, vegetables, beverages including coffee, tea, red wine, and dark chocolate are the important sources of these bioactive compounds. On the basis of their chemical structure, two categories of polyphenols are described: the flavonoids containing a common diphenylpropane skeleton (e.g., flavonoids, flavones, flavanols, flavonols, isoflavones, proanthocyanidins and anthocyanins); the non-flavonoids, mainly comprising mono-phenols alcohols (e.g., hydroxytyrosol) or stilbene phenolic acids (e.g., resveratrol).…”

“…On the basis of their chemical structure, two categories of polyphenols are described: the flavonoids containing a common diphenylpropane skeleton (e.g., flavonoids, flavones, flavanols, flavonols, isoflavones, proanthocyanidins and anthocyanins); the non-flavonoids, mainly comprising mono-phenols alcohols (e.g., hydroxytyrosol) or stilbene phenolic acids (e.g., resveratrol). [20] In the short-term, polyphenols are not essential for life such as vitamins, however, nowadays they are considered responsible for the beneficial effects of fruits and vegetables. Their potential role in the prevention and treatment of oxidative stress and inflammation has been investigated recently.…”

“…[21] In particular, polyphenols may present hepatoprotective effects by increasing the fatty acid oxidation and modulation of insulin resistance, oxidative stress and inflammation, which are the main pathogenetic factors linked to the progression from simple fat accumulation to NASH. [20] Several evidences in vitro, pre-clinical and emerging clinical trials reported beneficial effects on liver steatosis and its pathogenic and clinical setting. [20][21][22][23] Few clinical studies were focused on the polyphenols use in NAFLD patients.…”

“…[20] Several evidences in vitro, pre-clinical and emerging clinical trials reported beneficial effects on liver steatosis and its pathogenic and clinical setting. [20][21][22][23] Few clinical studies were focused on the polyphenols use in NAFLD patients. Three were undertaken with 500 mg and 600 mg resveratrol daily for 12 weeks, or 3000 mg daily for 8 weeks respectively.…”

Nutritional regulation of fibroblast growth factor 21: from macronutrients to bioactive dietary compounds

“…On the other hand, an anthocyanin-rich juice extract up-regulates PPARa activity in mice on a HFD and down-regulates lipogenic gene expression in liver by promoting FA consumption. Coffee polyphenols and resveratrol also induce FAO in rats through PPARa and PGC1a-dependent mechanisms [132]. Chalcones and flavokawain cardamonin type B inhibit lipid accumulation and adipocyte differentiation by increasing the phosphorylation of the ERK in the early phase of adipogenesis [133].…”