Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition: a link with insulin resistance

Background. Apelin is an adipokine with an intermediatory role in obesity and insulin resistance, which can be modified by dietary intake. Aims. In this study, we aimed to determine the association of the plasma fatty acid composition with apelin plasma concentration and gene expression in visceral (VAT) and subcutaneous (SAT) adipose tissues. Methods. In this cross-sectional study, we recruited 179 patients aged 19-75 years who were candidates for elective surgery. Through the surgery, SAT and VAT were collected to measure apelin gene expression. Anthropometric measurements, fasting blood samples, and dietary intakes were collected before surgery. Free fatty acids (FFAs) in fasting whole plasma were measured using gas chromatography with flame ionization detection. Linear regression models were used to estimate standardized β (STZ β ) showing the association of individual and total FFAs with apelin gene expression after adjustment for potential confounding variables. Results. In multivariable analysis, we observed a significant positive association of total plasma free fatty acids (FFAs) (STZ β = 0.241 , P = 0.006 ), saturated fatty acid (SFA) (STZ β = 0.336 , P < 0.001 ), and monounsaturated fatty acid (MUFA) (STZ β = 0.313 , P < 0.001 ) concentrations with apelin gene expression from VAT after controlling for age, sex, body mass index, homeostatic model assessment for insulin resistance (HOMA-IR), physical activity, and energy intake. In the SFA family, there was a direct association with plasma concentration of myristic acid (STZ β = 0.372 , P < 0.001 ), pentadecanoic acid ( STZ β = 0.252 , P = 0.002 ), and heptadecanoic acid (STZ β = 0.407 , P < 0.001 ) with apelin mRNA expression in VAT. There was no significant association between FFAs and apelin plasma concentration and SAT mRNA levels. Conclusions. In conclusion, circulating plasma FFAs, SFA, and MUFA had a positive association with apelin gene expression in VAT. It seems that plasma fatty acid composition may regulate apelin gene expression in VAT.

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Developmental and Tissue-Specific Involvement of Peroxisome Proliferator-Activated Receptor-α in the Control of Mouse Uncoupling Protein-3 Gene Expression

Endocrinology ◽

10.1210/en.2006-0226 ◽

2006 ◽

Vol 147 (10) ◽

pp. 4695-4704 ◽

Cited By ~ 14

Author(s):

Neus Pedraza ◽

Meritxell Rosell ◽

Joan Villarroya ◽

Roser Iglesias ◽

Frank J. Gonzalez ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Fatty Acids ◽

Fatty Acid ◽

Mrna Expression ◽

Uncoupling Protein ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ucp3 Gene ◽

Uncoupling Protein 3

Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor-α (PPARα) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPARα-null mice both in basal conditions and under the stimulus of starvation. In contrast, UCP3 mRNA is down-regulated in adult heart both in fed and fasted PPARα-null mice. This occurs despite the increased levels of free fatty acids caused by fasting in PPARα-null mice. In neonates, PPARα-null mice show impaired UCP3 mRNA expression in skeletal muscle in response to milk intake, and this is not a result of reduced free fatty acid levels. The murine UCP3 promoter is activated by fatty acids through either PPARα or PPARδ but not by PPARγ or retinoid X receptor alone. PPARδ-dependent activation could be a potential compensatory mechanism to ensure appropriate expression of UCP3 gene in adult skeletal muscle in the absence of PPARα. However, among transcripts from other PPARα and PPARδ target genes, only those acutely induced by milk intake in wild-type neonates were altered in muscle or heart from PPARα-null neonates. Thus, PPARα-dependent regulation is required for appropriate gene regulation of UCP3 as part of the subset of fatty-acid-responsive genes in neonatal muscle and heart.

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Fatty Acid Composition of Skeletal Muscle Membrane Phospholipids, Insulin Resistance and Obesity

Nutrition Today ◽

10.1097/00017285-199401000-00004 ◽

1994 ◽

Vol 29 (1) ◽

pp. 12-16 ◽

Cited By ~ 13

Author(s):

ARTEMIS P. SIMOPOULOS

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Acid Composition ◽

Muscle Membrane ◽

Membrane Phospholipids

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The effect of dietary fat on fatty acid composition, gene expression and vitamin status in pre-ruminant calves

Animal Feed Science and Technology ◽

10.1016/j.anifeedsci.2017.05.004 ◽

2017 ◽

Vol 229 ◽

pp. 32-42 ◽

Cited By ~ 3

Author(s):

C.Y. Tsai ◽

P. Rezamand ◽

W.I. Loucks ◽

C.M. Scholte ◽

M.E. Doumit

Keyword(s):

Gene Expression ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Acid Composition ◽

Dietary Fat ◽

Vitamin Status

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Dietary fat and insulin action in humans

British Journal Of Nutrition ◽

10.1017/s000711450000101x ◽

2000 ◽

Vol 83 (S1) ◽

pp. S91-S96 ◽

Cited By ~ 168

Author(s):

Bengt Vessby

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acids ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Linoleic Acid ◽

Insulin Sensitivity ◽

Acid Composition ◽

Δ5 Desaturase ◽

Reduced Activity

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16 : 0) and palmitoleic acids (16 : 1 n-7) and reduced levels of linoleic acid (18 : 2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20 : 3 n-6) and a reduced activity of the Δ5 desaturase, while the activities of the Δ9 and Δ6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of Δ5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.

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