Editorial: should <scp>NAFLD</scp> be included in the definition of Metabolic Syndrome?

Colosimo, Santo; Marchesini, Giulio

doi:10.1111/apt.17411

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…However, the proposed nomenclature concept has limitations in classifying subtypes of NAFLD due to insufficient data. It is important to highlight that metabolic syndrome and its components are strongly associated with NAFLD/MASLD ( 20 ). Therefore, metformin, a drug targeting various factors related to metabolic syndrome, such as fasting plasma glucose levels and waist circumference, may also alleviate NAFLD in the following ways.…”

Section: Nafldmentioning

confidence: 99%

Metformin: update on mechanisms of action on liver diseases

Ruan,

Wu,

Shi

et al. 2023

Front. Nutr.

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Substantial attention has been paid to the various effects of metformin on liver diseases; the liver is the targeted organ where metformin exerts its antihyperglycemic properties. In non-alcoholic fatty liver disease (NAFLD), studies have shown that metformin affects the ATP/AMP ratio to activate AMPK, subsequently governing lipid metabolism. The latest research showed that low-dose metformin targets the lysosomal AMPK pathway to decrease hepatic triglyceride levels through the PEN2-ATP6AP1 axis in an AMP-independent manner. Metformin regulates caspase-3, eukaryotic initiation factor-2a (eIF2a), and insulin receptor substrate-1 (IRS-1) in palmitate-exposed HepG2 cells, alleviating endoplasmic reticulum (ER) stress. Recent observations highlighted the critical association with intestinal flora, as confirmed by the finding that metformin decreased the relative abundance of Bacteroides fragilis while increasing Akkermansia muciniphila and Bifidobacterium bifidum. The suppression of intestinal farnesoid X receptor (FXR) and the elevation of short-chain fatty acids resulted in the upregulation of tight junction protein and the alleviation of hepatic inflammation induced by lipopolysaccharide (LPS). Additionally, metformin delayed the progression of cirrhosis by regulating the activation and proliferation of hepatic stellate cells (HSCs) via the TGF-β1/Smad3 and succinate-GPR91 pathways. In hepatocellular carcinoma (HCC), metformin impeded the cell cycle and enhanced the curative effect of antitumor medications. Moreover, metformin protects against chemical-induced and drug-induced liver injury (DILI) against hepatotoxic drugs. These findings suggest that metformin may have pharmacological efficacy against liver diseases.

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Section: Nafldmentioning

confidence: 99%

Metformin: update on mechanisms of action on liver diseases

Ruan,

Wu,

Shi

et al. 2023

Front. Nutr.

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“…Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD) [1], is a common condition that affects both adults and children, which is characterised by macrovesicular steatosis in ≥5% of hepatocytes, with no hepatocellular damage; metabolic dysfunction-associated steatohepatitis (MASH), also known as non-alcoholic steatohepatitis (NASH), is an advanced form of MASLD, identified by the presence of steatosis, hepatocyte ballooning, lobular inflammation, and fibrosis at histology [2]. People diagnosed with MASH experience a more severe progression of the disease, leading to advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC) [3]. It is estimated that approximately 25% of the adult population and 3-10% of children are diagnosed with MASLD, with the number increasing up to 40% in children and to 70% in adults who are obese [4,5].…”

Section: Introductionmentioning

confidence: 99%

Metformin and the Liver: Unlocking the Full Therapeutic Potential

Perazza,

Leoni,

Colosimo

et al. 2024

Metabolites

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Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes.

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Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility

Mambrini,

Grillo,

Colosimo

et al. 2024

Front. Nutr.

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Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a prevalent health concern, encompassing a wide spectrum of liver-related disorders. Insulin resistance, a key pathophysiological feature of MASLD, can be effectively ameliorated through dietary interventions. The Mediterranean diet, rich in whole grains, fruits, vegetables, legumes, and healthy fats, has shown promising results in improving insulin sensitivity. Several components of the Mediterranean diet, such as monounsaturated fats and polyphenols, exert anti-inflammatory and antioxidant effects, thereby reducing hepatic steatosis and inflammation. Furthermore, this dietary pattern has been associated with a higher likelihood of achieving MASLD remission. In addition to dietary modifications, physical exercise, particularly resistance exercise, plays a crucial role in enhancing metabolic flexibility. Resistance exercise training promotes the utilization of fatty acids as an energy source. It enhances muscle glucose uptake and glycogen storage, thus reducing the burden on the liver to uptake excess blood glucose. Furthermore, resistance exercise stimulates muscle protein synthesis, contributing to an improved muscle-to-fat ratio and overall metabolic health. When implemented synergistically, the Mediterranean diet and resistance exercise can elicit complementary effects in combating MASLD. Combined interventions have demonstrated additive benefits, including greater improvements in insulin resistance, increased metabolic flexibility, and enhanced potential for MASLD remission. This underscores the importance of adopting a multifaceted approach encompassing dietary modifications and regular physical exercise to effectively manage MASLD. This narrative review explores the biological mechanisms of diet and physical exercise in addressing MASLD by targeting insulin resistance and decreased metabolic flexibility.

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Editorial: should NAFLD be included in the definition of Metabolic Syndrome?

Abstract: LINKED CONTENTThis article is linked to Fu et al paper. To view this article, visit https://doi.org/10.1111/apt.17397

Cited by 3 publications

References 14 publications

Metformin: update on mechanisms of action on liver diseases

Metformin: update on mechanisms of action on liver diseases

Metformin and the Liver: Unlocking the Full Therapeutic Potential

Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility

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