Understanding the Alterations in Lipid Metabolism in NAFLD Progression: Current Trends and Future Directions

Mungamuri, Sathish Kumar; Sinha, Sukesh Narayan; Javvadi, Yamini

doi:10.1615/critrevoncog.2020035839

Cited by 11 publications

(9 citation statements)

References 91 publications

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“…NAFLD includes a simple fatty liver and nonalcoholic steatohepatitis (NASH), together with fibrosis and inflammation [ 48 , 49 , 50 , 51 ]. Patients with T2DM have higher risk of NAFLD, and the presence of T2DM tends to aggravate NAFLD [ 52 , 53 , 54 ]. It was also reported that patients with T2DM had higher risk for liver cirrhosis and hepatocellular carcinoma [ 55 ].…”

Section: Sglt2 Inhibitors Have Some Favorable Effects On Nonalcohomentioning

confidence: 99%

Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

Kaneto

Obata

Kimura

et al. 2021

IJMS

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Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic β-cell function and insulin sensitivity. SGLT2 inhibitors ameliorate fatty liver and reduce visceral fat mass. Furthermore, it has been noted that SGLT2 inhibitors have cardio-protective and renal protective effects in addition to their glucose-lowering effect. In addition, several kinds of SGLT2 inhibitors are used in patients with type 1 diabetes mellitus as an adjuvant therapy to insulin. Taken together, SGLT2 inhibitors have amazing multifaceted effects that are far beyond prediction like some emerging magical medicine. Thereby, SGLT2 inhibitors are very promising as relatively new anti-diabetic drugs and are being paid attention in various aspects. It is noted, however, that SGLT2 inhibitors have several side effects such as urinary tract infection or genital infection. In addition, we should bear in mind the possibility of diabetic ketoacidosis, especially when we use SGLT2 inhibitors in patients with poor insulin secretory capacity.

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Section: Sglt2 Inhibitors Have Some Favorable Effects On Nonalcohomentioning

confidence: 99%

Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

Kaneto

Obata

Kimura

et al. 2021

IJMS

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“…In physiological conditions, the liver converts excess fatty acid into triglycerides, their hepatic storage form, through de-novo lipogenesis (DNL) [ 47 ]. To compensate this storage, PPARα regulates the conversion of fatty acids into energy through the mitochondria fatty acid β-oxidation, a pathway reducing hepatic fat accumulation and secreting very-low-density lipoprotein (VLDL) exporting lipids to other tissues [ 47 ]. However, in pathological conditions and excess lipids in the liver, the existing pathways to compensate this excess no longer work.…”

Section: Involvement Of Myokines In Nafld Pathologymentioning

confidence: 99%

Myokines: Crosstalk and Consequences on Liver Physiopathology

Bourie¹,

Potier²,

Pinget³

et al. 2023

Nutrients

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Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease mainly characterized by the hepatic accumulation of lipid inducing a deregulation of β-oxidation. Its advanced form is non-alcoholic steatohepatitis (NASH), which, in addition to lipid accumulation, induces hepatocellular damage, oxidative stress and fibrosis that can progress to cirrhosis and to its final stage: hepatocellular carcinoma (HCC). To date, no specific therapeutic treatment exists. The implications of organ crosstalk have been highlighted in many metabolic disorders, such as diabetes, metabolic-associated liver diseases and obesity. Skeletal muscle, in addition to its role as a reservoir and consumer of energy and carbohydrate metabolism, is involved in this inter-organs’ communication through different secreted products: myokines, exosomes and enzymes, for example. Interestingly, resistance exercise has been shown to have a beneficial impact on different metabolic pathways, such as lipid oxidation in different organs through their secreted products. In this review, we will mainly focus on myokines and their effects on non-alcoholic fatty liver disease, and their complication: non-alcoholic steatohepatitis and HCC.

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“…1). 24 The other genetic variants that have been associated with NAFLD include the genes regulating fibrogenesis, oxidative stress, and insulin signaling (Table 1). Besides, aberrant expression of several adipokines and cytokines are also associated with NAFLD onset and progression.…”

Section: Introductionmentioning

confidence: 99%

Evolution of Non-alcoholic Fatty Liver Disease to Liver Cancer: Insights from Genome-wide Association Studies

Mungamuri¹,

Gupta²,

Rao³

et al. 2023

Gene Expr

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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease, affecting a quarter of the world's population. The spectrum of NAFLD ranges from simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma (HCC). Multiple factors are involved in the pathogenesis and progression of NAFLD, wherein genetic, epigenetic, environmental, gut-microbiome, and dietary factors play a substantial role. Robust genome-wide association studies (GWAS) have recently identified several genetic alterations contributing to NAFLD progression to liver cancer. This review describes the most critical genetic variations identified in various genes that modulate NAFLD pathogenesis. As expected, NAFLD shows gene variations that regulate or influence hepatocyte lipid metabolism. In addition to polymorphisms in genes that regulate insulin signaling, fibrosis, inflammation, and oxidative stress, cytokine/chemokine-expressing genes also participate in NAFLD pathogenesis. GWAS helped us distinguish genetic polymorphisms that modulate steatosis, fibrosis, or both in NAFLD patients. Identifying genetic factors predisposing an individual to NAFLD helps stratify people at high risk and aids in imparting preventive strategies early in life. Such studies should also help in adopting prevention strategies and targeted treatment regimes.

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Understanding the Alterations in Lipid Metabolism in NAFLD Progression: Current Trends and Future Directions

Cited by 11 publications

References 91 publications

Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

Myokines: Crosstalk and Consequences on Liver Physiopathology

Evolution of Non-alcoholic Fatty Liver Disease to Liver Cancer: Insights from Genome-wide Association Studies

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