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Fiber Type and Subcellular-Specific Analysis of Lipid Droplet Content in Skeletal Muscle
Published on: June 8, 2022
Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice
Kathryn C Jackson1, Lindsay M Wohlers, Richard M Lovering
1Univ. of Maryland, School of Public Health, Dept. of Kinesiology, College Park, MD 20742, USA.
Abstract:
Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) female mice compared with age-matched ovary-intact adult female mice (sham). The OVX mice exhibited significant increases in body weight, visceral, and inguinal fat mass compared with sham mice. OVX mice also had significant increases in skeletal muscle intramyocellular lipids (IMCL) compared with the sham animals, which corresponded to significant increases in the protein content of the fatty acid transporters CD36/FAT and FABPpm. A targeted metabolic profiling approach identified significantly lower levels of specific acyl carnitine species and various amino acids in skeletal muscle from OVX mice compared with the sham animals, suggesting a potential dysfunction in lipid and amino acid metabolism, respectively. Basal and maximal mitochondrial oxygen consumption rates were significantly impaired in skeletal muscle fibers from OVX mice compared with sham animals. Collectively, these data indicate that loss of ovarian function results in increased IMCL storage that is coupled with alterations in mitochondrial function and changes in the skeletal muscle metabolic profile.
Insights
Loss of ovarian function in mice leads to increased body fat and intramyocellular lipids (IMCL) in skeletal muscle. This is associated with impaired mitochondrial function and altered metabolic profiles, contributing to metabolic disease risk.
Area of Science:
- Endocrinology
- Metabolic disease
- Skeletal muscle physiology
Background:
- Ovarian function loss is linked to metabolic disease risk.
- Skeletal muscle plays a key role in glucose homeostasis.
- Previous research suggests lipid and mitochondrial dysfunction in skeletal muscle following ovarian function loss.
Purpose of the Study:
- To investigate skeletal muscle metabolic dysfunction in ovariectomized (OVX) mice.
- To compare OVX mice with age-matched, ovary-intact (sham) controls.
- To identify specific metabolic alterations using an integrative approach.
Main Methods:
- Ovariectomy (OVX) in mice to mimic ovarian function loss.
- Measurement of body weight, fat mass, and skeletal muscle intramyocellular lipids (IMCL).
- Analysis of fatty acid transporter protein expression (CD36/FAT, FABPpm).
- Targeted metabolic profiling of acyl carnitines and amino acids.
- Assessment of mitochondrial oxygen consumption rates in skeletal muscle fibers.
Main Results:
- OVX mice showed increased body weight, visceral, and inguinal fat mass.
- Skeletal muscle IMCL content and fatty acid transporter protein levels were elevated in OVX mice.
- Reduced levels of specific acyl carnitines and amino acids were observed in OVX mice skeletal muscle.
- Mitochondrial basal and maximal oxygen consumption rates were significantly impaired in OVX mice skeletal muscle.
Conclusions:
- Ovarian function loss leads to increased IMCL accumulation in skeletal muscle.
- Mitochondrial function is compromised in skeletal muscle following ovarian function loss.
- Altered skeletal muscle metabolic profiles, including lipid and amino acid metabolism, are associated with ovarian function loss, potentially contributing to metabolic disease.
