Sexually dimorphic metabolic effects of a high fat diet on knee osteoarthritis in mice.

Autor: Griffin TM; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA. Tim-Griffin@omrf.org.; Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA. Tim-Griffin@omrf.org.; University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. Tim-Griffin@omrf.org., Lopes EBP; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.; Labcorp Drug Development, Indianapolis, IN, USA., Cortassa D; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.; VA Oklahoma City Health Care, Oklahoma City, OK, USA., Batushansky A; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.; Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Be'er Sheva, 84105, Israel., Jeffries MA; Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA.; University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA., Makosa D; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.; University of Western Australia, Perth, Western Australia, Australia., Jopkiewicz A; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.; Panier Group, Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9B, 50931, Cologne, Germany., Mehta-D'souza P; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA., Komaravolu RK; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.; Immunology Center of Georgia, Augusta University, Augusta, GA, 30912, USA., Kinter MT; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
Jazyk: angličtina
Zdroj: Biology of sex differences [Biol Sex Differ] 2024 Dec 05; Vol. 15 (1), pp. 103. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1186/s13293-024-00680-6
Abstrakt: Background: Women have a higher risk of developing osteoarthritis (OA) than men, including with obesity. To better understand this disparity, we investigated sex differences in metabolic and inflammatory factors associated with OA using a diet-induced mouse model of obesity. We hypothesized that 20 weeks of high-fat diet (HFD) would induce sexually dimorphic changes in both systemic and local risk factors of knee OA.
Methods: Male and female C57BL/6J mice were fed Chow or HFD from 6 to 26 weeks of age (n = 12 per diet and sex). We performed broad metabolic phenotyping, 16 S gut microbiome analysis, targeted gene expression analysis of synovium-infrapatellar fat tissue, targeted gene expression and proteomic analysis of articular cartilage, chondrocyte metabolic profiling, and OA histopathology. Two-way ANOVA statistics were utilized to determine the contribution of sex and diet and their interaction on outcomes.
Results: Mice fed HFD weighed 1.76-fold (p < 0.0001) and 1.60-fold (p < 0.0001) more than male and female Chow cohorts, respectively, with both sexes reaching similar body fat levels (male: 43.9 ± 2.2%; female: 44.1 ± 3.8%). HFD caused greater cartilage pathology (p < 0.024) and synovial hyperplasia (p < 0.038) versus Chow in both sexes. Cartilage pathology was greater in male versus female mice (p = 0.048), and only male mice developed osteophytes with HFD (p = 0.044). Both sexes exhibited metabolic inflexibility on HFD, but only male mice developed glucose intolerance (p < 0.0001), fatty liver (p < 0.0001), and elevated serum amylase (p < 0.0001) with HFD versus Chow. HFD treatment caused sex-dependent differences in gut microbiota beta diversity (p = 0.01) and alteration in specific microbiome clades, such as a HFD-dependent reduction in abundance of Bifidobacterium only in male mice. In knee synovium and infrapatellar fat tissue, HFD upregulated the expression of pro-inflammatory and pro-fibrotic genes predominantly in female mice. In cartilage, lipid metabolism proteins were more abundant with HFD in male mice, whereas proteins involved in glycolysis/gluconeogenesis and biosynthesis of amino acids were greater in cartilage of female mice. Sex-dependent metabolic differences were observed in cartilage from young, healthy mice prior to pubertal maturation, but not in primary juvenile chondrocytes studied in vitro.
Conclusions: HFD induced numerous sex differences in metabolic and inflammatory outcomes, especially in joint tissues, suggesting that sex-specific cellular processes are involved during development of early-stage OA with obesity.
Competing Interests: Declarations. Ethics approval and consent to participate: The animal experiments were conducted according to protocol approved by the Oklahoma Medical Research Foundation Institutional Animal Care and Use Committee (protocol #14–54 and #17–60). Consent for publication: Not applicable. Competing interests: TMG has a patent application pending entitled, “COMPOSITIONS AND METHODS FOR TREATING OSTEOARTHRITIS USING A CD14 INHIBITOR” (#18/411,242).
(© 2024. The Author(s).)
Databáze: MEDLINE
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