Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance
Abstract
Increasing evidence suggests that reduced adipose tissue mitochondrial content is associated with the pathogenesis of type 2 diabetes. These investigations have utilized severely insulin-resistant rodent models. Thus, it is difficult to ascertain the potential mechanisms that initiate these changes and whether reductions in adipose mitochondria are an initiating event in the development of impaired glucose homeostasis. Thus, we sought to determine the time course of high-fat diet-induced reductions of mitochondrial content in epididymal adipose tissue in relation to changes in purported mediators of mitochondrial biogenesis and the development of impaired glucose homeostasis. Male Wistar rats were fed a high-fat diet ( approximately 59% of kcals from fat) for 2, 4, or 6 wk. Six weeks of high-fat feeding resulted in reductions in CORE I, COX IV, cytochrome c, HSP60, relative mtDNA copy number, and PGC-1alpha expression. These changes were not associated with decreases in eNOS and AMPK or increases in markers of oxidative stress. Interestingly, ex vivo treatment of adipose tissue cultures with palmitate led to decreases in PGC-1alpha expression and COX IV and CORE I protein content as observed in vivo. Thus, the high-fat diet-induced reductions in adipose tissue mitochondrial proteins may be mediated by increases in plasma fatty acids. Importantly, reductions in adipose tissue mitochondrial content occurred after the development of impaired glucose homeostasis. Thus, reductions in adipose tissue mitochondrial proteins are most likely not a causal event in the development of impaired glucose homeostasis.
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Both genetic and diet-induced obesity result in decreased mitochondrial density and OXPHOS activity in adipose tissue, potentially contributing to adipose tissue dysfunction and exacerbation of insulin resistance.
“Conversely, both genetic and dietinduced obesity result in decreased mitochondrial density and OXPHOS activity in adipose tissue (127, 177, 189 -191), potentially contributing to adipose tissue dysfunction and exacerbation of insulin resistance.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [191]
White adipocyte mitochondrial content is decreased in both rodent and human obesity and correlates with insulin resistance that accompanies obesity.
“White adipocyte mitochondrial content is decreased in both rodent and human obesity (177, 188 -191) and correlates with insulin resistance that accompanies obesity.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [191]
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- Authors
- Sutherland, L. N., Capozzi, L. C., Turchinsky, N. J., Bell, R. C., & Wright, D. C.
- Affiliations
- University of Alberta (CA)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-11
- Volume
- 295
- Issue
- 5
- Pages
- E1076-E1083
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2144632432
- Cited by
- 147
- References
- 32
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 3 · 2020: 13 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 8 · 2014: 16 · 2013: 17 · 2012: 8
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- high-fat diet, mitochondrial biogenesis, PGC-1α, impaired glucose homeostasis, impaired glucose tolerance, type 2 diabetes, epididymal adipose tissue, palmitate, plasma fatty acids, mitochondrial proteins, cytochrome c oxidase subunit IV, cytochrome c, mitochondrial DNA copy number, oxidative stress, AMPK, endothelial nitric oxide synthase
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Blood Glucose, Body Weight, Dietary Fats, DNA, Mitochondrial, Epididymis, Fatty Acids, Nonesterified, Insulin, Male, Mitochondria, Transcription Factors, RNA-Binding Proteins, Rats, Wistar, Glucose Intolerance, Oxidative Stress, Palmitic Acid, Mitochondrial Proteins, Rats, Nitric Oxide Synthase Type III, Adipose Tissue, White, AMP-Activated Protein Kinases
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