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Cited by 967Fatty Acid Research and HealthDiet, Metabolism, and DiseaseLipid metabolism and biosynthesis

Influence of Dietary Fat Composition on Development of Insulin Resistance in Rats: Relationship to Muscle Triglyceride and ω-3 Fatty Acids in Muscle Phospholipid

Storlien, Leonard H, Jenkins, Arthur B, Chisholm, Donald J, Pascoe, Wendy S, Khouri, Sue, Kraegen, Edward W·1991·Diabetes
DOI 10.2337/diab.40.2.280
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Abstract

High levels of some but not all dietary fats lead to insulin resistance in rats. The aim of this study was to investigate the important determinants underlying this observation. Insulin action was assessed with the euglycemic clamp. Diets high in saturated, monounsaturated (ω-9), or polyunsaturated (ω-6) fatty acids led to severe insulin resistance; glucose infusion rates [GIR] to maintain euglycemia at ∼1000 pM insulin were 6.2 ± 0.9, 8.9 ± 0.9, and 9.7 ± 0.4 mg · kg−1 · min−1, respectively, versus 16.1 ± 1.0 mg · kg−1 · min−1 in chow-fed controls. Substituting 11% of fatty acids in the polyunsaturated fat diet with long-chain ω-3 fatty acids from fish oils normalized insulin action (GIR 15.0 ± 1.3 mg · kg−1 · min−1). Similar replacement with short-chain ω-3 (α-linolenic acid, 18:3ω3) was ineffective in the polyunsaturated diet (GIR 9.9 ± 0.5 mg · kg−1 · min−1) but completely prevented the insulin resistance induced by a saturated-fat diet (GIR 16.0 ± 1.5 mg · kg−1 · min−1) and did so in both the liver and peripheral tissues. Insulin sensitivity in skeletal muscle was inversely correlated with mean muscle triglyceride accumulation (r = 0.95 and 0.86 for soleus and red quadriceps, respectively; both P = 0.01). Furthermore, percentage of long-chain ω-3 fatty acid in phospholipid measured in red quadriceps correlated highly with insulin action in that muscle (r = 0.97). We conclude that 1) the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats; 2) impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose–fatty acid cycle involvement; and 3) long-chain ω-3 fatty acids in phospholipid of skeletal muscle may be important for efficient insulin action.

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Crossref · 10.2337/diab.40.2.280

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  • In animals, a high-fat diet increases intramuscular fat content, which correlates with both the severity and the temporal development of insulin resistance.

    “(iv) in animals, a high fat diet causes an increase in intramuscular fat content, which correlates closely both with the severity and temporal development of insulin resistance [75, 76];”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [75]

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Authors
Storlien, L. H., Jenkins, A. B., Chisholm, D. J., Pascoe, W. S., Khouri, S., & Kraegen, E. W.
Affiliations
Garvan Institute of Medical Research (AU)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1991-02-01
Volume
40
Issue
2
Pages
280-289
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.40.2.280
OpenAlex
W2122248435
Cited by
967
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 13 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 13 · 2019: 16 · 2018: 17 · 2017: 14 · 2016: 37 · 2015: 34 · 2014: 24 · 2013: 25 · 2012: 32
FWCI
21.06
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of New South Wales
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
dietary fat composition, insulin resistance, omega-3 fatty acids, n-3 long-chain polyunsaturated fatty acids, fish oil, alpha-linolenic acid, skeletal muscle insulin sensitivity, saturated fatty acids, omega-6 fatty acids, omega-9 fatty acids, glucose-fatty acid cycle, high-fat diet, euglycemic clamp
MeSH terms
Animals, Dietary Fats, Fatty Acids, Monounsaturated, Fatty Acids, Unsaturated, Insulin, Insulin Resistance, Male, Muscles, Phospholipids, Rats, Inbred Strains, Triglycerides, Fatty Acids, Omega-3, Rats

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