RT Journal Article
T1 Male Brown Fat–Specific Double Knockout of IGFIR/IR: Atrophy, Mitochondrial Fission Failure, Impaired Thermogenesis, and Obesity
A1 Viana-Huete, Vanesa
A1 Guillén Viejo, Carlos
A1 García, Gema
A1 Fernández, Silvia
A1 García Aguilar, Ana
A1 Kahn, Carl Ronald
A1 Benito De Las Heras, Manuel R.
AB It is unknown how the lack of insulin receptor (IR)/insulinlike growth factor I receptor (IGFIR) in a tissue-specific manner affects brown fat development and mitochondrial integrity and function, as well as its effect on the redistribution of the adipose organ and the metabolic status. To address this important issue, we developed IR/IGFIR double-knockout (DKO) in a brown adipose tissue-specific manner. Lack of those receptors caused severe brown fat atrophy, enhanced beige cell clusters in inguinal fat; loss of mitochondrial mass; mitochondrial damage related to cristae disruption; and the loss of proteins involved in autophagosome formation, mitophagy, mitochondrial quality control, and dynamics and thermogenesis. More important, DKO mice showed an impaired thermogenesis upon cold exposure, based on a failure in the mitochondrial fission mechanisms and a much lower uncoupling protein 1 transcription rate and content. As a result, DKO mice under normal conditions showed an obesity susceptibility, revealed by increased body fat mass and insulin resistance. Upon consumption of a high-fat diet, DKO mice displayed frank obesity, as shown by increased body weight, increased adiposity, insulin resistance, hyperinsulinemia, and hypertriglyceridemia, all consistent with a metabolic syndrome. Collectively, our data suggest a cause-and-effect relationship between failure in brown fat thermogenesis and increased adiposity and obesity.
PB Endocrine Society
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/115669
UL https://hdl.handle.net/20.500.14352/115669
LA eng
NO Viana-Huete V, Guillén C, García G, Fernández S, García-Aguilar A, Kahn CR, Benito M. Male Brown Fat-Specific Double Knockout of IGFIR/IR: Atrophy, Mitochondrial Fission Failure, Impaired Thermogenesis, and Obesity. Endocrinology. 2018 Jan 1;159(1):323-340. doi: 10.1210/en.2017-00738. PMID: 29040448; PMCID: PMC6283434.
NO Instituto de Salud Carlos III
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 8 abr 2025