Abstract
Mice that lack phosphatidylethanolamine N-methyltransferase (Pemt(-/-) mice) are protected from high-fat (HF) diet-induced obesity. HF-fed Pemt(-/-) mice show higher oxygen consumption and heat production, indicating that more energy might be utilized for thermogenesis and might account for the resistance to diet-induced weight gain. To test this hypothesis, HF-fed Pemt(-/-) and Pemt(+/+) mice were challenged with acute cold exposure at 4°C. Unexpectedly, HF-fed Pemt(-/-) mice developed hypothermia within 3 h of cold exposure. In contrast, chow-fed Pemt(-/-) mice, possessing similar body mass, maintained body temperature. Lack of PEMT did not impair the capacity for thermogenesis in skeletal muscle or brown adipose tissue. Plasma catecholamines were not altered by Pemt genotype, and stimulation of lipolysis was intact in brown and white adipose tissue of Pemt(-/-) mice. HF-fed Pemt(-/-) mice also developed higher systolic blood pressure, accompanied by reduced cardiac output. Choline supplementation reversed the cold-induced hypothermia in HF-fed Pemt(-/-) mice with no effect on blood pressure. Plasma glucose levels were ∼50% lower in HF-fed Pemt(-/-) mice compared with Pemt(+/+) mice. Choline supplementation normalized plasma hypoglycemia and the expression of proteins involved in gluconeogenesis. We propose that cold-induced hypothermia in HF-fed Pemt(-/-) mice is linked to plasma hypoglycemia due to compromised hepatic glucose production.
Highlights
Mice that lack phosphatidylethanolamine Nmethyltransferase (Pemt؊/؊ mice) are protected from highfat (HF) diet-induced obesity
Cold exposure is widely used to Abbreviations: ATGL, adipose TG lipase; BAT, brown adipose tissue; C/EBP, CCAAT/enhancer-binding protein ; DIO, diet-induced obesity; FABP4, fatty acid binding protein 4; HF, high-fat; HFCS, choline-supplemented high-fat; HSL, hormone-sensitive lipase; PC, phosphatidylcholine; PE, phosphatidylethanolamine; Phosphatidylethanolamine N-methyltransferase (PEMT), phosphatidylethanolamine N-methyltransferase; PEPCK, phosphoenolpyruvate carboxykinase; PGC1␣, PPAR␥ coactivator 1␣; T3, triiodothyronine; T4, thyroxine; TGH, TG hydrolase; UCP, uncoupling protein; WAT, white adipose tissue
When fed the HF diet for 10 weeks, PemtϪ/Ϫ mice exhibit higher oxygen consumption than Pemt+/+ mice [9], indicating that higher energy expenditure for heat production might account for the resistance of HF-fed PemtϪ/Ϫ mice to DIO
Summary
Mice that lack phosphatidylethanolamine Nmethyltransferase (Pemt؊/؊ mice) are protected from highfat (HF) diet-induced obesity. HF-fed Pemt؊/؊ mice show higher oxygen consumption and heat production, indicating that more energy might be utilized for thermogenesis and might account for the resistance to diet-induced weight gain. To test this hypothesis, HF-fed Pemt؊/؊ and Pemt+/+ mice were challenged with acute cold exposure at 4°C. Journal of Lipid Research Volume 56, 2015 1701 determine the capability for thermogenesis [12] Upon cold exposure, both skeletal muscle-mediated shivering thermogenesis and brown adipose tissue (BAT)-mediated nonshivering thermogenesis are activated to maintain the core body temperature [12]. Intolerance to cold exposure might reflect inadequate heat production or a defective heart to accommodate the cold-activated catabolism [12]
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