Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse

Daniel M. Kelly, Samia Akhtar, Donna J. Sellers, Vakkat Muraleedharan, Kevin S. Channer, T. Hugh Jones

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Abstract

Testosterone deficiency is commonly associated with obesity, metabolic syndrome, type 2 diabetes and their clinical consequences—hepatic steatosis and atherosclerosis. The testicular feminised mouse (non-functional androgen receptor and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat diet, whereas androgen-replete XY littermate controls do not. Testosterone treatment ameliorates these effects, although the underlying mechanisms remain unknown. We compared the influence of testosterone on the expression of regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver, abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle, liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein lipase required for fatty acid uptake was only reduced in subcutaneous adipose tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is associated with insulin resistance was increased in visceral adipose tissue and cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and liver tissue. Master regulator nuclear receptors involved in metabolism—Liver X receptor expression was suppressed in all tissues except visceral adipose tissue, whereas PPARγ was lower in abdominal subcutaneous and visceral adipose tissue and PPARα only in abdominal subcutaneous. Testosterone treatment improved the expression (androgen receptor independent) of some targets but not all. These exploratory data suggest that androgen deficiency may reduce the buffering capability for glucose uptake and utilisation in abdominal subcutaneous and muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill and uptake of excess glucose and triglycerides into visceral adipose tissue, liver and arterial walls.

Original languageEnglish
Pages (from-to)504-515
Number of pages12
JournalEndocrine
Volume54
Issue number2
DOIs
Publication statusPublished - 1 Nov 2016

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Intra-Abdominal Fat
Lipid Metabolism
Testosterone
Adipose Tissue
Glucose
Muscles
Liver
Abdominal Subcutaneous Fat
Abdominal Muscles
Peroxisome Proliferator-Activated Receptors
Fatty Acids
Subcutaneous Tissue
Androgen Receptors
Androgens
Cholesterol
Stearoyl-CoA Desaturase
Lipoprotein Lipase
Subcutaneous Fat
High Fat Diet
Apolipoproteins E

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Kelly, Daniel M. ; Akhtar, Samia ; Sellers, Donna J. ; Muraleedharan, Vakkat ; Channer, Kevin S. ; Jones, T. Hugh. / Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse. In: Endocrine. 2016 ; Vol. 54, No. 2. pp. 504-515.
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Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse. / Kelly, Daniel M.; Akhtar, Samia; Sellers, Donna J.; Muraleedharan, Vakkat; Channer, Kevin S.; Jones, T. Hugh.

In: Endocrine, Vol. 54, No. 2, 01.11.2016, p. 504-515.

Research output: Contribution to journalArticleResearchpeer-review

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