Hulett, Nicholas A.;
Knaub, Leslie A.;
Hull, Sara E.;
Pott, Gregory B.;
Peelor, Rick;
Miller, Benjamin F.;
Shankar, Kartik;
Rudolph, Michael C.;
Reusch, Jane E. B.;
Scalzo, Rebecca L.
Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats
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Medientyp:
E-Artikel
Titel:
Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats
Beteiligte:
Hulett, Nicholas A.;
Knaub, Leslie A.;
Hull, Sara E.;
Pott, Gregory B.;
Peelor, Rick;
Miller, Benjamin F.;
Shankar, Kartik;
Rudolph, Michael C.;
Reusch, Jane E. B.;
Scalzo, Rebecca L.
Beschreibung:
<jats:p>Men are diagnosed with type 2 diabetes at lower body mass indexes than women; the role of skeletal muscle in this sex difference is poorly understood. Type 2 diabetes impacts skeletal muscle, particularly in females who demonstrate a lower oxidative capacity compared to males. To address mechanistic differences underlying this sex disparity, we investigated skeletal muscle mitochondrial respiration in female and male rats in response to chronic high-fat, high-sugar (HFHS) diet consumption. Four-week-old Wistar Rats were fed a standard chow or HFHS diet for 14 weeks to identify sex-specific adaptations in mitochondrial respirometry and characteristics, transcriptional patterns, and protein profiles. Fat mass was greater with the HFHS diet in both sexes when controlled for body mass (p < 0.0001). Blood glucose and insulin resistance were greater in males (p = 0.01) and HFHS-fed rats (p < 0.001). HFHS-fed males had higher mitochondrial respiration compared with females (p < 0.01 sex/diet interaction). No evidence of a difference by sex or diet was found for mitochondrial synthesis, dynamics, or quality to support the mitochondrial respiration sex/diet interaction. However, transcriptomic analyses indicate sex differences in nutrient handling. Sex-specific differences occurred in PI3K/AKT signaling, PPARα/RXRα, and triacylglycerol degradation. These findings may provide insight into the clinical sex differences in body mass index threshold for diabetes development and tissue-specific progression of insulin resistance.</jats:p>