Loss of Trim28 in muscle alters mitochondrial signalling but not systemic metabolism

J Endocrinol. 2023 Oct 9;259(2):e230210. doi: 10.1530/JOE-23-0210. Print 2023 Nov 1.

Abstract

Type 2 diabetes mellitus (T2DM), a condition characterised by insulin resistance (IR) and skeletal muscle mitochondrial abnormalities, is a leading cause of death in developed societies. Much work has postulated that improving pathways linked to mitochondrial health, including autophagy, may be a potential avenue to prevent or treat T2DM. Given the recent data indicating a role for tripartite motif-containing 28 (TRIM28) in autophagy and mitochondrial pathways, we investigated whether muscle-specific deletion of TRIM28 might impact on obesity, glucose tolerance, and IR in mice. We studied two different muscle-specific (MCK-cre and ACTA1-cre-ERT2) TRIM28 knockout models, which were phenotyped during and after being fed a chow or high-fat diet (HFD). Whilst muscle-specific deletion of TRIM28 in both models demonstrated alterations in markers of mitochondrial activity and autophagy in skeletal muscle, we did not observe major impacts on the majority of metabolic measures in these mice. Specifically, we demonstrate that deletion of TRIM28 in skeletal muscle of mice during (MCK-cre) or post-development (ACTA1-cre-ERT2) does not prevent HFD-induced obesity or glucose intolerance. These findings are consistent with those reported previously in relation to autophagy and mitochondria in other cell types, and thus warrant further study into the biological role TRIM28 has in relation to mitochondrial function.

Keywords: TRIM28; glucose tolerance; metabolism; mitochondria; skeletal muscle.

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / metabolism
  • Diet, High-Fat / adverse effects
  • Glucose Intolerance* / metabolism
  • Insulin Resistance* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria, Muscle / metabolism
  • Muscle, Skeletal / metabolism
  • Obesity / metabolism
  • Tripartite Motif-Containing Protein 28 / metabolism

Substances

  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28