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Publications in Nature Metabolism by NOMIS researchers

NOMIS Researcher(s)

Published in

January 29, 2024

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

Research field(s)
Biochemistry & Molecular Biology, Genetics & Heredity

NOMIS Researcher(s)

Published in

June 1, 2022

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Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

NOMIS Researcher(s)

Published in

July 1, 2020

For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that infectious diseases are complex, multisystem conditions, and a holistic understanding will be necessary to maximize survival. For COVID-19 and all other infectious diseases, metabolic processes are intimately connected to the mechanisms of disease pathogenesis and the resulting pathology and pathophysiology, as well as the host defence response to the infection. Here, I examine the relationship between metabolism and COVID-19. I discuss why preexisting metabolic abnormalities, such as type 2 diabetes and hypertension, may be important risk factors for severe and critical cases of infection, highlighting parallels between the pathophysiology of these metabolic abnormalities and the disease course of COVID-19. I also discuss how metabolism at the cellular, tissue and organ levels might be harnessed to promote defence against the infection, with a focus on disease-tolerance mechanisms, and speculate on the long-term metabolic consequences for survivors of COVID-19.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology