Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/20/4438 |
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| author | Nicholas A. Hulett Leslie A. Knaub Sara E. Hull Gregory B. Pott Rick Peelor Benjamin F. Miller Kartik Shankar Michael C. Rudolph Jane E. B. Reusch Rebecca L. Scalzo |
| author_facet | Nicholas A. Hulett Leslie A. Knaub Sara E. Hull Gregory B. Pott Rick Peelor Benjamin F. Miller Kartik Shankar Michael C. Rudolph Jane E. B. Reusch Rebecca L. Scalzo |
| author_sort | Nicholas A. Hulett |
| collection | DOAJ |
| description | 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 (<i>p</i> < 0.0001). Blood glucose and insulin resistance were greater in males (<i>p</i> = 0.01) and HFHS-fed rats (<i>p</i> < 0.001). HFHS-fed males had higher mitochondrial respiration compared with females (<i>p</i> < 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. |
| first_indexed | 2024-03-10T20:59:16Z |
| format | Article |
| id | doaj.art-0cffd8de027a40fd8f74a5171bfb0f9f |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T20:59:16Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-0cffd8de027a40fd8f74a5171bfb0f9f2023-11-19T17:38:52ZengMDPI AGNutrients2072-66432023-10-011520443810.3390/nu15204438Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in RatsNicholas A. Hulett0Leslie A. Knaub1Sara E. Hull2Gregory B. Pott3Rick Peelor4Benjamin F. Miller5Kartik Shankar6Michael C. Rudolph7Jane E. B. Reusch8Rebecca L. Scalzo9Division of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USADivision of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USADivision of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USARocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO 80045, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USADepartment of Pediatrics, Section of Nutrition, University of Colorado School of Medicine (UCSOM), Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Physiology, Harold Hamm Diabetes Center, Oklahoma University Health Sciences Center, Oklahoma City, OK 73104, USADivision of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USADivision of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USAMen 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 (<i>p</i> < 0.0001). Blood glucose and insulin resistance were greater in males (<i>p</i> = 0.01) and HFHS-fed rats (<i>p</i> < 0.001). HFHS-fed males had higher mitochondrial respiration compared with females (<i>p</i> < 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.https://www.mdpi.com/2072-6643/15/20/4438sex differencestype 2 diabetesmitochondrial respirationskeletal musclemetabolism |
| spellingShingle | Nicholas A. Hulett Leslie A. Knaub Sara E. Hull Gregory B. Pott Rick Peelor Benjamin F. Miller Kartik Shankar Michael C. Rudolph Jane E. B. Reusch Rebecca L. Scalzo Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats Nutrients sex differences type 2 diabetes mitochondrial respiration skeletal muscle metabolism |
| title | Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats |
| title_full | Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats |
| title_fullStr | Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats |
| title_full_unstemmed | Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats |
| title_short | Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats |
| title_sort | sex differences in the skeletal muscle response to a high fat high sucrose diet in rats |
| topic | sex differences type 2 diabetes mitochondrial respiration skeletal muscle metabolism |
| url | https://www.mdpi.com/2072-6643/15/20/4438 |
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