A tissue-specific increase in lipogenesis in rat brown adipose tissue in hypothyroidism

Abstract

1. Rats were made hypothyroid by feeding them with propylthiouracil together with a low-iodine diet for 4 weeks. 2. [U-14C]Glucose conversion into fatty acids was substantially enhanced in brown adipocytes isolated from hypothyroid rats. Incorporation of 3H2O into fatty acids in vivo was enhanced in hypothyroidism in interscapular brown fat, but not in epididymal white fat or in liver. Hypothyroidism increased the activities of fatty acid synthase and ATP citrate lyase in brown, but not in white, adipocytes. 3. Glycolytic flux in brown adipocytes, quantified by [3-3H]glucose detritiation, was increased by hypothyroidism. This change was accompanied by increased maximum activity of phosphofructokinase. In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells. It is suggested that in the brown adipocyte the overall conversion of glucose into fatty acids is enhanced in thyroid deficiency, but that this change is muted in the white adipocyte, possibly because of limitation of glucose transport. 4. Fatty acid synthesis in brown adipocytes from hypothyroid animals was considerably less sensitive to inhibition by exogenous fatty acids than is the process in cells from euthyroid animals. Consequently, the effect of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acid.

Preclinical studies on the toxicology, pharmacokinetics and safety of K1-70TM a human monoclonal autoantibody to the TSH receptor with TSH antagonist activity

“…Hypothyroidism causes changes in the handling of long chain fatty acids by white and brown adipocytes. In brown adipocytes fatty acid synthesis from glucose is substantially enhanced in hypothyroidism [25]. In this study, the large clear vacuoles seen in the cytoplasm of brown adipose tissue in the rats were consistent with lipid storage vacuoles, which in turn was consistent with enhanced fatty acid synthesis.…”

Hormonal and Nutritional Regulation of Lipogenic Enzyme mRNA Levels in Rat Primary White and Brown Adipocytes

“…In vivo, lipogenesis is usually highest in hypothyroid BAT and is reduced by T3 treatment (14)(15)(16). Expression of ACC, FAS, and S14 mRNAs follows the same pattern (25).…”

A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations

“…Numerous studies have indicated that hypothyroidism is a risk factor for nonalcoholic fatty liver disease and results in metabolic syndrome ( 32 – 34 ). In addition, the effects of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acids ( 35 ). FASN is an enzyme involved in fatty acid biosynthesis ( 36 ).…”