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Combined weight loss and exercise training improved insulin sensitivity by altering lipid distribution within muscle cells and remodeling intermuscular adipose tissue (IMAT). This highlights IMAT

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Area of Science:

  • Metabolic Physiology
  • Exercise Science
  • Obesity Research

Background:

  • Subcellular lipid accumulation and intermuscular adipose tissue (IMAT) are linked to insulin resistance.
  • The effects of combined weight loss and exercise on lipid localization and IMAT cellularity remain unclear.

Purpose of the Study:

  • To investigate the impact of a 3-month supervised weight loss and exercise intervention on subcellular lipid distribution and IMAT cellular composition in adults with obesity.
  • To correlate these changes with improvements in insulin sensitivity.

Main Methods:

  • A 3-month supervised weight loss and exercise training intervention was conducted in 21 adults with obesity.
  • Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp.
  • Vastus lateralis muscle biopsies were analyzed for lipidomics and single-nuclei RNA sequencing; IMAT cellular composition was evaluated.

Main Results:

  • The intervention led to significant reductions in body weight and fat, and increases in peak oxygen consumption (VO2 peak) and insulin sensitivity.
  • Lipidomics revealed decreased sarcolemmal and nuclear triglycerides, increased nuclear diacylglycerols, and increased cytosolic sphingolipids.
  • IMAT analysis showed altered cellular composition, with increased fibro-adipogenic progenitors, vascular cells, and macrophages, and decreased preadipocytes.

Conclusions:

  • Improvements in insulin sensitivity were dissociated from changes in total muscle diacylglycerol and sphingolipid levels.
  • Subcellular lipid redistribution and IMAT remodeling play crucial roles in enhancing insulin sensitivity following weight loss and exercise.
  • The study highlights the complex interplay between lipid metabolism, IMAT, and metabolic health.