ArticleAmerican journal of physiology. Endocrinology and metabolism2017
High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent adipose expansion in C57BL/6J mice.
Article in American journal of physiology. Endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 82 citations in OpenAlex.
- Sex Differences in Angiogenic Ligand and Receptor Protein Expression During Adipose Tissue Expansion and Regression.Cellular and molecular bioengineering · 2026Article
- Decreased degree of adipocyte differentiation in visceral adipose tissue contributes to metabolic dysfunction-associated steatotic liver disease.Nature communications · 2026Article
- Urokinase Plasminogen Activator Deficiency Delays the Development of Obesity and Metabolic Sequelae.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Plasma-targeted proteomic and lipidomic profiling of MASLD, MASH, and hepatitis C virus infection.Clinical proteomics · 2026Article
- Low protein-induced-FGF-21 signaling remodels adipose tissue on reduced markers of senescence during aging.GeroScience · 2026Article
- Surgical removal of visceral adipose tissue has therapeutic benefit in male APPFrontiers in endocrinology · 2026Article
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.Nature medicine · 2025Article
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- Transcriptome remodelling and changes in growth and cardiometabolic phenotype result following Grb10a knockdown in the early life of the zebrafish.Cellular and molecular life sciences : CMLS · 2025Article
- MMP3 at the crossroads: Linking molecular pathways to disease diagnosis and therapy.Pharmacological research · 2025Review
- Article
- Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity.Cell metabolism · 2025Article
- Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- Sex-based differences in short- and longer-term diet-induced metabolic heart disease.American journal of physiology. Heart and circulatory physiology · 2024Article
- The pathophysiology of visceral adipose tissues in cardiometabolic diseases.Biochemical pharmacology · 2024Review
- Genetic regulatory effects in response to a high-cholesterol, high-fat diet in baboons.Cell genomics · 2024Article
- Macronutrient-differential dietary pattern impacts on body weight, hepatic inflammation, and metabolism.Frontiers in nutrition · 2024Article
- Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity-The Case of BBS Obesity.Nutrients · 2023Review
- Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease.International journal of molecular sciences · 2023Review
- Article
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4 authors at 1 institution in 1 country.
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Abstract
Increased adipocyte size is hypothesized to signal the recruitment of adipose progenitor cells (APCs) to expand tissue storage capacity. To investigate depot and sex differences in adipose growth, male and female C57BL/6J mice (10 wk-old) were challenged with high-fat (HF) or low-fat (LF) diets (D) for 14 wk. The HFD increased gonadal (GON) depot weight by adipocyte hypertrophy and hyperplasia in females but hypertrophy alone in males. In both sexes, inguinal (ING) adipocytes were smaller than GON, and depot expansion was due to hypertrophy. Matrix metalloproteinase 3 (Mmp3), an antiadipogenic factor, and its inhibitor Timps modulate the extracellular matrix remodeling needed for depot expansion. Mmp3 mRNA was depot different (ING > GON), higher in females than males and mainly expressed in APCs. In males, HFD-induced obesity increased tissue and APC Mmp3 mRNA levels and MMP3 protein and enzymatic activity. In females however, HFD significantly decreased MMP3 protein without affecting its mRNA levels. MMP3 activity also decreased (significant in ING). Timp4 mRNA was expressed mainly in adipocytes, and HFD-induced obesity tended to increase the ratio of TIMP4 to MMP3 protein in females, whereas it decreased it in males. Overexpression of Mmp3 in 3T3-L1 preadipocytes or rhMMP3 protein added to primary human preadipocytes inhibited differentiation, whereas rhTIMP4 improved adipogenesis and attenuated the inhibitory effect of rhMMP3. These data suggest that HFD-induced obesity downregulates APC MMP3 expression to trigger adipogenesis, and adipocyte TIMP4 may modulate this process to regulate hyperplastic vs. hypertrophic adipose tissue expansion, fat distribution, and metabolic health in a sex- and depot-dependent manner.
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