Axelrod 2023 MiP2023

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MiPschool 2023

Axelrod 2023 MiP2023

Axelrod Christopher L
Skeletal muscle mitochondrial dynamics in obesity and type 2 diabetes.

Link: MiP2023 Obergurgl AT

Axelrod Christopher L (2023)

Event: MiP2023 Obergurgl AT

Authors: Axelrod Christopher L, Kirwan John P

Obesity mediates the onset of lipid-induced insulin resistance, increasing the risk of type 2 diabetes. The inability of mitochondria to maintain core functions such as ATP synthesis, redox homeostasis, organelle quality control, and/or preservation of inheritance is proposed to link obesity-related insulin resistance to the onset and progression of type 2 diabetes, yet evidence remains elusive. To parse out the contributions of obesity versus peripheral insulin resistance, healthy weight adults were infused with an intralipid solution followed by evaluation of skeletal muscle mitochondrial function. The lipid infusion reduced insulin sensitivity and dampened mitochondrial membrane potential while increasing markers of mitochondrial fission and increasing the presence of autophagic vesicles, consistent with activation of the quality control machinery. Despite this, respiratory capacity and mitochondrial content were unaltered. From these studies, we concluded that activation of mitochondrial fission and quality control were early events in the onset of insulin resistance to defend cellular energy homeostasis. Subsequently, we conducted a cross-sectional analysis of individuals across the insulin sensitivity spectrum. We observed that markers of fission and quality control were markedly altered in patients with obesity and type 2 diabetes relative to obesity alone and healthy weight despite no apparent differences in respiratory capacity. Mitochondrial volume was incrementally lower in patients with obesity and type 2 diabetes relative to healthy weight. Collectively, we conclude that preservation of bioenergetic function in patients with obesity and type 2 diabetes is achieved by chronic activation of the quality control machinery which occurs at the expense of mitochondrial volume.

β€’ O2k-Network Lab: US LA Baton Rouge Noland RC


Christopher L. Axelrod and John P. Kirwan
Integrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA

Labels: Pathology: Diabetes, Obesity 

Organism: Human  Tissue;cell: Skeletal muscle 

Event: Oral 

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