To investigate the possibility that environmental temperature may exert physiologically significant direct, local effects on subcutaneous adipose tissue temperatures, and its secretion of leptin, we exposed healthy males (n=12) to repeated cold-water immersion (study 1), and also incubated surgically removed human subcutaneous adipose tissue samples (n=7) at 27°, 32° and 37°C (study 2). In vivo immersions were conducted over 15 days (60–90 min at 18°C). Regional body temperatures and plasma leptin concentrations were measured before and during immersion. Acute cold exposure suppressed plasma leptin concentration (25 min: −14%, 60 min: −22%, P=0.0001), whilst repeated cold-water immersion was associated with an increase of plasma leptin concentration relative to test day 1 (+19% day 8, +13% day 15, overall P=0.03). Leptin secretion in vitro decreased 3.7-fold as the incubation temperature decreased from 37° to 27°C (P=0.001). In a compartmental model of leptin turnover in vivo, the measured (local) temperature effect on leptin secretion in vitro was more than able to account for the observed cold-induced decrease in leptin concentration in vivo. We therefore conclude that acute and repeated cold-water immersions have separate and opposing effects on circulating leptin concentrations in humans. Under our experimental conditions, the local effects of reduced subcutaneous adipose tissue temperature may be a more important contributor to the acute effects observed in vivo, than the sympathetically mediated suppression of leptin secretion.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Atterhog JH, Carlens P, Granberg PO, Wallenberg LR (1975) Cardiovascular and renal responses to acute cold exposure in water-loaded man. Scand J Clin Lab Invest 35:311–317
Bing C, Frankish HM, Pickavance L, Wang Q, Hopkins DF, Stock MJ, Williams G (1998) Hyperphagia in cold-exposed rats is accompanied by decreased plasma leptin but unchanged hypothalamic NPY. Am J Physiol 274:R62–R68
Coruzzi P, Biggi A, Musiari L, Ravanetti C, Novarini A (1986) Renal hemodynamics and natriuresis during water immersion in normal humans. Pflugers Arch 407:638–642
Deng C, Moinat M, Curtis L, Nadakal A, Preitner F, Boss O, Assimacopoulos JF, Seydoux J, Giacobino JP (1997) Effects of beta-adrenoceptor subtype stimulation on obese gene messenger ribonucleic acid and on leptin secretion in mouse brown adipocytes differentiated in culture. Endocrinology 138:548–552
Epstein M, Levinson R, Loutzenhiser R (1976) Effects of water immersion on renal hemodynamics in normal man. J Appl Physiol 41:230–233
Evans BA, Agar L, Summers RJ (1999) The role of the sympathetic nervous system in the regulation of leptin synthesis in C57BL/6 mice. FEBS Lett 444:149–154 [erratum in FEBS Lett (1999) 451(2):214]
Garibotto G, Russo R, Franceschini R, Robaudo C, Saffioti S, Sofia A, Rolandi E, Deferrari G, Barreca T (1998) Inter-organ leptin exchange in humans. Biochem Biophys Res Commun 247:504–509
Gottschling-Zeller H, Birgel M, Scriba D, Blum WF, Hauner H (1999) Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-alpha and transforming growth factor-beta1. Eur J Endocrinol 141:436–442
Hardie LJ, Rayner DV, Holmes S, Trayhurn P (1996) Circulating leptin levels are modulated by fasting cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem Biophys Res Commun 223:660–665
Havel PJ (2000) Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. Proc Nutr Soc 59:359–371
International Organisation for Standardisation (1992) Evaluation of thermal strain by physiological measurements. ISO 9886:1992 [E] Geneva, Switzerland
Jenkins AB, Samaras K, Gordon MA, Snieder H, Spector T, Campbell LV (2001) Lack of heritability of circulating leptin concentration in humans after adjustment for body size and adiposity using a physiological approach. Int J Obes 25:1625–1632
Katch FI, McArdle WD (1973) Prediction of body density from simple anthropometric measurements in college-age men and women. Hum Biol 45: 445–454
Katzmarzyk PT, Leonard WR (1998) Climatic influences on human body size and proportions: ecological adaptations and secular trends. Am J Phys Anthropol 106:483–503
Martinez AE, Perez M, Martinez JA (1998) Induction of hypothermia hypoglycemia and hyperinsulinemia after acute leptin immunoneutralization in overnight fasted mice. Int J Mol Med 2:681–683
Meyer C, Robson D, Rackovsky N, Nadkarni V, Gerich J (1997) Role of the kidney in human leptin metabolism. Am J Physiol 273:E903–E907
Moinat M, Deng C, Muzzin P, Assimacopoulos-Jeannet F, Seydoux J, Dulloo AG, Giacobino JP (1995) Modulation of obese gene expression in rat brown and white adipose tissues. FEBS Lett 373:131–134
Neale MC (1997) Mx; Statistical Modeling. http://www.vipbg.vcu.edu/~mx. Cited 8 April 1998
Neale MC, Walters EE, Eaves LJ, Maes HH, Kendler KS (1994) Multivariate genetic analysis of twin-family data on fears: Mx models. Behav Genet 24:119–139
Peino R, Pineiro V, Gualillo O, Menendez C, Brenlla J, Casabiell X, Dieguez C, Casanueva FF (2000) Cold exposure inhibits leptin secretion in vitro by a direct and non-specific action on adipose tissue. Eur J Endocrinol 142:195–199
Rayner DV, Trayhurn P (2001) Regulation of leptin production: sympathetic nervous system interactions. J Mol Med 79:8–20
Stocks JM, Patterson MJ, Hyde DE, Jenkins AB, Mittleman KD, Taylor NAS (2004) Cold-water acclimation does not modify whole-body fluid regulation during subsequent cold-water immersion. Eur J Appl Physiol (in press)
Ricci MR, Fried SK, Mittleman KD (2000) Acute cold exposure decreases plasma leptin in women. Metabolism 49:421–423
Roberts D (1978) Climate and human variability. Cummings, Menlo Park, Calif.
Seidell JC, Bakker CJ, van der Kooy K (1990) Imaging techniques for measuring adipose-tissue distribution—a comparison between computed tomography and 15-T magnetic resonance. Am J Clin Nutr 51:953–957
Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF (1996) Nocturnal rise of leptin in lean obese and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 97:1344–1347
Sramek P, Ulicny B, Jansky L, Hosek V, Zeman V, Janakova H (1993) Changes of body fluids and ions in cold-adapted subjects. Sports Med Training Rehabil 4:195–203
Stehling O, Doring H, Nuesslein HB, Olbort M, Schmidt I (1997) Leptin does not reduce body fat content but augments cold defense abilities in thermoneutrally reared rat pups. Pflugers Arch 434:694–697
Trayhurn P, Duncan JS, Rayner DV (1995) Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system. Biochem J 311:729–733
Trayhurn P, Hoggard N, Mercer JG, Rayner DV (1999) Leptin: fundamental aspects. Int J Obes Relat Metab Disord 23 [Suppl 1]:22–28
Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, Arner P (19980 Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 47:913–917
Webb P (1992) Temperatures of skin subcutaneous tissue muscle and core in resting men in cold comfortable and hot conditions. Eur J Appl Physiol 64:471–476
Westerterp-Plantenga MS (1999) Effects of extreme environments on food intake in human subjects. Proc Nutr Soc 58:791–798
Zeyl A, Lim-Fraser M, Lapsys NM, Cooney G, Taylor NAS, Jenkins AB (2000) Effects of temperature on metabolism and leptin secretion in human subcutaneous adipose tissue in vitro. In: 2000 Pre-Olympic Congress: International Congress on Sport Science, Sport Medicine and Physical Education, The Australasian Society for the Study of Obesity, Brisbane, Queensland, Australia, 7–12 September 2000, p 99
Zhang HH, Kumar S, Barnett AH, Eggo MC (1999) Intrinsic site-specific differences in the expression of leptin in human adipocytes and its autocrine effects on glucose uptake. J Clin Endocrinol Metab 84:2550–2556
This research was funded, in part, by a grant from the National Health and Medical Research Council (Australia). A. Zeyl held a post-graduate research scholarships from the University of Wollongong, Australia. J.M. Stocks was funded by ABSTUDY, Department of Employment, Education and Training, Australia. We gratefully acknowledge Sister Sheena McGhee for her clinical assistance, and Olivier de Hon, Lieske Hofland, Matt Allen and Paul Argerakis for their technical assistance during data collection.
About this article
Cite this article
Zeyl, A., Stocks, J.M., Taylor, N.A.S. et al. Interactions between temperature and human leptin physiology in vivo and in vitro. Eur J Appl Physiol 92, 571–578 (2004). https://doi.org/10.1007/s00421-004-1084-7
- Cold acclimation
- Cold immersion
- Tissue temperature