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Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich's ataxia mouse model.

ABSTRACT: Friedreich's ataxia (FA) is a neurodegenerative disease resulting from a mutation in the FXN gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications. RNA-seq analysis revealed altered expression of inflammation, angiogenesis, and fibrosis genes. Diabetes-like traits, including larger adipocytes, immune cell infiltration, and increased lactate production, were observed in vWAT. FXN downregulation in cultured adipocytes mirrored vWAT diabetes-like features, showing metabolic shifts toward glycolysis and lactate production. Metagenomic analysis indicated a reduction in fecal butyrate-producing bacteria, known to exert antidiabetic effects. A butyrate-enriched diet restrained vWAT abnormalities and mitigated diabetes features in KIKO mice. Our work emphasizes the role of vWAT in FA-related metabolic issues and suggests butyrate as a safe and promising adjunct for FA management.

SUBMITTER: Turchi R

PROVIDER: S-EPMC10494209 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich's ataxia mouse model.

Turchi Riccardo R Sciarretta Francesca F Ceci Veronica V Tiberi Marta M Audano Matteo M Pedretti Silvia S Panebianco Concetta C Nesci Valentina V Pazienza Valerio V Ferri Alberto A Carotti Simone S Chiurchiù Valerio V Mitro Nico N Lettieri-Barbato Daniele D Aquilano Katia K

iScience 20230828 10

Friedreich's ataxia (FA) is a neurodegenerative disease resulting from a mutation in the <i>FXN</i> gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications. RNA-seq analysis revealed altered expression of inflammation, angiogenesis, and fi ...[more]

PMID: 37701569

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Project description:BackgroundFat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.Methods and resultsTo first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE(-/-) mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.ConclusionsOur results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.

Dataset Information

Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich's ataxia mouse model.

Publications

Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich's ataxia mouse model.

Similar Datasets

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