Microvesicular Steatosis in Individuals with Obesity: a Histological Marker of Non-alcoholic Fatty Liver Disease Severity

Germano, Carlos Wustemberg; Mega, Paulo Ferreira; Mattosinho, Thiago Jordão Almeida Prado; Dias, Luana Leite Castilho; Gestic, Martinho Antônio; Chaim, Felipe David Mendonça; Callejas-Neto, Francisco; Chaim, Élinton Adami; Cazzo, Everton

doi:10.1007/s11695-023-06467-9

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Compared with macrovesicular steatosis, microvesicular steatosis has been suggested to be an independent predictor of advanced liver injury in MASH ( 48 ). It has been shown that a defect in fatty acid oxidation results in the accumulation of lipids in the cytosol and the formation of megamitochondria, one of the hallmark features of microvesicular steatosis ( 47 – 50 ). Expression of hepatic CD36 , a fatty acid transporter correlated with the presence of macrovesicular steatosis, was decreased in DIO-MASH FGF15 INT-KO mice.…”

Section: Discussionmentioning

confidence: 99%

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance

Bozadjieva-Kramer,

Shin,

et al. 2024

JCI Insight

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Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15 –/– mice have limited our understanding of gut-specific FGF15’s role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction–associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis–inducing diet to control and intestine-derived FGF15-knockout (FGF15 INT-KO ) mice. Control and FGF15 INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15 INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.

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Section: Discussionmentioning

confidence: 99%

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance

Bozadjieva-Kramer,

Shin,

et al. 2024

JCI Insight

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“…On the contrary, microvesicular steatosis has been found to co-exist with higher frequencies of severe macrovesicular steatosis, inflammation, cellular injury, and hepatocyte ballooning, features that are commonly found in NASH livers [39]. Thus, microvesicular steatosis could be considered as a significant prognostic factor of the transition from simple steatosis to steatohepatitis [40].…”

Section: Structural Changes In Lds Affecting Nafld Progressionmentioning

confidence: 99%

Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets

Mastoridou,

Goussia,

Kanavaros

et al. 2023

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of lipids in the form of lipid droplets in more than 5% of hepatocytes. It is regarded as a range of diverse pathologies, including simple steatosis and steatohepatitis. The structural characteristics of lipid droplets, along with their protein composition, mainly including perilipins, have been implicated in the etiology of the disease. These proteins have garnered increasing attention as a pivotal regulator since their levels and distinct expression appear to be associated with the progression from simple steatosis to steatohepatitis. Perilipins are target proteins of chaperone-mediated autophagy, and their degradation is a prerequisite for lipolysis and lipophagy to access the lipid core. Both lipophagy and chaperone-mediated autophagy have significant implications on the development of the disease, as evidenced by their upregulation during the initial phases of simple steatosis and their subsequent downregulation once steatosis is established. On the contrary, during steatohepatitis, the process of chaperone-mediated autophagy is enhanced, although lipophagy remains suppressed. Evidently, the reduced levels of autophagic pathways observed in simple steatosis serve as a defensive mechanism against lipotoxicity. Conversely, in steatohepatitis, chaperone-mediated autophagy fails to compensate for the continuous generation of small lipid droplets and thus cannot protect hepatocytes from lipotoxicity.

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Fibrotic NASH in Individuals with Obesity: a Cross-sectional Analysis of the Prevalence of this Significant Milestone of Disease Progression and Accuracy of a Non-invasive Marker for its Screening

de Souza Echeverria,

Mounzer,

Gestic

et al. 2023

OBES SURG

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Microvesicular Steatosis in Individuals with Obesity: a Histological Marker of Non-alcoholic Fatty Liver Disease Severity

Cited by 5 publications

References 26 publications

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance

Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets

Fibrotic NASH in Individuals with Obesity: a Cross-sectional Analysis of the Prevalence of this Significant Milestone of Disease Progression and Accuracy of a Non-invasive Marker for its Screening

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