Abstract
Homeothermic animals, including humans, live by adapting to changes in ambient temperature. Numerous studies have demonstrated cold exposure (at approximately 5°C) improves glucose tolerance despite reducing insulin secretion and increasing energy expenditure. To determine the effects of a small reduction in ambient temperature on energy metabolism, we compared two groups of mice; one exposed to a cool environment (20°C) and the other maintained in a near-thermoneutral environment (25°C) for 10 days. Both glucose-induced insulin secretion and glucose response were significantly impaired in mice exposed to a cool environment. In the cool temperature-exposed mice, skin temperatures were reduced, and plasma norepinephrine levels were increased, suggesting that impairment of insulin secretion was facilitated by induction of sympathetic nervous activity due to skin cooling. In addition, expression of GLUT4 mRNA was increased significantly in inguinal subcutaneous adipose tissue (IWAT) but not in epididymal or brown adipose tissue or skeletal muscle in these mice. Moreover, expression of Dok1, a molecule linked to activation of insulin receptors in adipocyte hypertrophy, and Cd36, a molecule related to NEFA uptake, were also increased at mRNA and/or protein levels only in IWAT of the cool temperature-exposed mice. Fatty acid synthesis was also facilitated, and fat weights were increased only in IWAT from mice kept at 20°C. These results suggest that a small reduction in ambient temperature can affect glucose homeostasis through regulation of insulin secretion and preferentially enhances fat storage in IWAT. These adaptations can be interpreted as preparation for a further reduction in ambient temperature.
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Bartness TJ, Demas GE, Song CK (2002) Seasonal changes in adiposity: the roles of the photoperiod, melatonin and other hormones, and sympathetic nervous system. Exp Biol Med (Maywood) 227:363–376
Bunout D, Barrera G, de la Maza P, Gattas V, Hirsch S (2003) Seasonal variation in insulin sensitivity in healthy elderly people. Nutrition 19:310–316
Desvergne B, Michalik L, Wahli W (2006) Transcriptional regulation of metabolism. Physiol Rev 86:465–514
Festuccia WT, Oztezcan S, Laplante M, Berthiaume M, Michel C, Dohgu S, Denis RG, Brito MN, Brito NA, Miller DS, Banks WA, Bartness TJ, Richard D, Deshaies Y (2008) Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status. Endocrinology 149:2121–2130
Florant GL, Porst H, Peiffer A, Hudachek SF, Pittman C, Summers SA, Rajala MW, Scherer PE (2004) Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris). J Comp Physiol B 174:633–639
Gasparetti AL, de Souza CT, Pereira-da-Silva M, Oliveira RL, Saad MJ, Carneiro EM, Velloso LA (2003) Cold exposure induces tissue-specific modulation of the insulin-signalling pathway in Rattus norvegicus. J Physiol 552:149–162
Gilon P, Henquin JC (2001) Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. Endocr Rev 22:565–604
Hosooka T, Noguchi T, Kotani K, Nakamura T, Sakaue H, Inoue H, Ogawa W, Tobimatsu K, Takazawa K, Sakai M, Matsuki Y, Hiramatsu R, Yasuda T, Lazar MA, Yamanashi Y, Kasuga M (2008) Dok1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPAR-gamma phosphorylation. Nat Med 14:188–193
Ishii H, Suzuki H, Baba T, Nakamura K, Watanabe T (2001) Seasonal variation of glycemic control in type 2 diabetic patients. Diabetes Care 24:1503
Levy-Marchal C, Patterson C, Green A (1995) Variation by age group and seasonality at diagnosis of childhood IDDM in Europe. The EURODIAB ACE Study Group. Diabetologia 38:823–830
MacDonald MJ, Liston L, Carlson I (1987) Seasonality in glycosylated hemoglobin in normal subjects. Does seasonal incidence in insulin-dependent diabetes suggest specific etiology? Diabetes 36:265–268
Masaki T, Yoshimatsu H, Chiba S, Sakata T (2000) Impaired response of UCP family to cold exposure in diabetic (db/db) mice. Am J Physiol Regul Integr Comp Physiol 279:R1305–R1309
Mrosovsky N, Faust IM (1985) Cycles of body fat in hibernators. Int J Obes 9(Suppl 1):93–98
Nakamura K, Morrison SF (2007) Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 292:R127–R136
Padaiga Z, Tuomilehto J, Karvonen M, Dahlquist G, Podar T, Adojaan B, Urbonaite B, Zalinkevicius R, Brigis G, Virtala E, Kohtamaki K, Cepaitis Z, Tuomilehto-Wolf E (1999) Seasonal variation in the incidence of Type 1 diabetes mellitus during 1983 to 1992 in the countries around the Baltic Sea. Diabet Med 16:736–743
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839
Scott EM, Grant PJ (2006) Neel revisited: the adipocyte, seasonality and type 2 diabetes. Diabetologia 49:1462–1466
Shibata H, Perusse F, Vallerand A, Bukowiecki LJ (1989) Cold exposure reverses inhibitory effects of fasting on peripheral glucose uptake in rats. Am J Physiol 257:R96–R101
Shimizu Y, Nikami H, Tsukazaki K, Machado UF, Yano H, Seino Y, Saito M (1993) Increased expression of glucose transporter GLUT-4 in brown adipose tissue of fasted rats after cold exposure. Am J Physiol 264:E890–E895
Smith OL, Davidson SB (1982) Shivering thermogenesis and glucose uptake by muscles of normal or diabetic rats. Am J Physiol 242:R109–R115
Vallerand AL, Frim J, Kavanagh MF (1988) Plasma glucose and insulin responses to oral and intravenous glucose in cold-exposed humans. J Appl Physiol 65:2395–2399
Vallerand AL, Lupien J, Bukowiecki LJ (1983) Interactions of cold exposure and starvation on glucose tolerance and insulin response. Am J Physiol 245:E575–E581
Vallerand AL, Perusse F, Bukowiecki LJ (1987) Cold exposure potentiates the effect of insulin on in vivo glucose uptake. Am J Physiol 253:E179–E186
Vallerand AL, Zamecnik J, Jones PJ, Jacobs I (1999) Cold stress increases lipolysis, FFA Ra and TG/FFA cycling in humans. Aviat Space Environ Med 70:42–50
Yang X, Smith U (2007) Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer? Diabetologia 50:1127–1139
Acknowledgments
This work was supported by grants to M.T. from the Ministry of Education, Culture, Sports, Science, and Technology in Japan and Hayama Center for Advanced Studies. We thank M. Kasuga for providing the Dok1 antibody. We also wish to thank N. Fukuta and A. Fukuda for technical assistance during the study.
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Uchida, K., Shiuchi, T., Inada, H. et al. Metabolic adaptation of mice in a cool environment. Pflugers Arch - Eur J Physiol 459, 765–774 (2010). https://doi.org/10.1007/s00424-010-0795-3
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DOI: https://doi.org/10.1007/s00424-010-0795-3