Increased Fatty Acid Uptake and Altered Fatty Acid Metabolism in Insulin-Resistant Muscle of Obese Zucker Rats
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Altered muscle fatty acid (FA) metabolism may contribute to the presence of muscle insulin resistance in the genetically obese Zucker rat. To determine whether FA uptake and disposal are altered in insulin-resistant muscle, we measured palmitate uptake, oxidation, and incorporation into di- and triglycerides in isolated rat hindquarters, as well as muscle plasma membrane fatty acid–binding protein (FABPPM) content of lean (n = 16, fa/+) and obese (n = 15, fa/fa) Zucker rats (12 weeks of age). Hindquarters were perfused with 7 mmol/l glucose, 1,000 μmol/l albumin-bound palmitate, and albumin-bound [1-14C]palmitate at rest (no insulin). Glucose uptake was 42% lower in the obese than in the lean rats and indicated the presence of muscle insulin resistance. Fractional and total rates of palmitate uptake were 42 and 74% higher in the obese than in the lean rats and were associated with higher muscle FABPPM content (r2 = 0.69, P < 0.05). The percentage of palmitate oxidized was not significantly different between groups. FA disposal to storage was altered according to fiber type. When compared with lean rats, the rate of triglyceride synthesis in red muscle was 158% higher in obese rats, and the rate of palmitate incorporation into diglycerides in white muscle was 93% higher in obese rats. Pre- and postperfusion muscle triglyceride levels were higher in both red and white muscles of the obese rats. These results show that increased FA uptake and altered FA disposal to storage may contribute to the development of muscle insulin resistance in obese Zucker rats.
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In some animal models of obesity, skeletal muscle shows a metabolic profile characterized by reduced glucose uptake and glucose oxidation, altered partitioning of fatty acids that are incorporated into triglycerides, and reduced oxygen consumption.
“In some animal models of obesity such as in obese Zucker rats or ob/ob mice, skeletal muscle shows a metabolic profile characterized by reduced glucose uptake and glucose oxidation, altered partitioning of fatty acids that are incorporated into triglycerides, and reduced oxygen consumption (14 -18).”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [18]
The Results and Discussion report lower glucose uptake in obese Zucker rats, cite a finding of lower basal glucose oxidation, and describe increased triglyceride synthesis in red muscle. But the Results state that resting oxygen uptake was not significantly different between obese and lean rats, so this paper does not support the reduced-oxygen-consumption part of the claim. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn some animal models of obesity such as obese Zucker rats or ob/ob mice, skeletal muscle shows a metabolic profile characterized by reduced glucose uptake and glucose oxidation, altered partitioning of fatty acids, insulin resistance and reduced oxygen consumption.
“In some animal models of obesity such as in obese Zucker rats or ob/ob mice, skeletal muscle shows a metabolic profile characterized by reduced glucose uptake and glucose oxidation, altered partitioning of fatty acids that are incorporated into triglycerides, or oxidized, insulin resistance and reduced oxygen consumption (38-43”
From Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism (2003) · cites this paper as [42]
The Abstract reports reduced glucose uptake, insulin resistance, and altered fatty-acid uptake and storage in obese Zucker rat muscle. The Discussion cites a prior finding of lower basal glucose oxidation, but also notes a contrasting finding under insulin stimulation. The Substrate exchange across the hindquarter section reports that resting oxygen uptake was not significantly different between obese and lean rats, rather than reduced; this study did not examine ob/ob mice. Page numbers are unavailable in our copy. (LLM, conf=0.90)
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- Authors
- Turcotte, L. P., Swenberger, J. R., Zavitz Tucker, M., & Yee, A. J.
- Affiliations
- University of Southern California (US)
- Department of Kinesiology and University of Southern California Diabetes Center, University of Southern California, Los Angeles, Califonia
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-06-01
- Volume
- 50
- Issue
- 6
- Pages
- 1389-1396
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2167135215
- Cited by
- 100
- References
- 49
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Southern California
- National Institutes of Health (5r29ar045168-04)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 45168)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- muscle insulin resistance, fatty acid uptake, fatty acid metabolism, palmitate oxidation, fatty acid storage, triglyceride synthesis, diacylglycerol synthesis, muscle fiber type, glucose uptake, obesity, Zucker rats
- MeSH terms
- Fatty Acid-Binding Protein 7, Animals, Carrier Proteins, Diglycerides, Fatty Acids, Female, Hindlimb, Insulin Resistance, Neoplasm Proteins, Nerve Tissue Proteins, Obesity, Oxidation-Reduction, Palmitates, Rats, Zucker, Thinness, Triglycerides, Blotting, Western, Muscle, Skeletal, Fatty Acid-Binding Proteins, Rats
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