Physiological role for leptin in the control of thermal conductance.
OBJECTIVE
To investigate the role played by leptin in thermoregulation, we studied the effects of physiological leptin replacement in leptin-deficient ob/ob mice on determinants of energy balance, thermogenesis and heat retention under 3 different ambient temperatures.


METHODS
The effects of housing at 14 °C, 22 °C or 30 °C on core temperature (telemetry), energy expenditure (respirometry), thermal conductance, body composition, energy intake, and locomotor activity (beam breaks) were measured in ob/ob mice implanted subcutaneously with osmotic minipumps at a dose designed to deliver a physiological replacement dose of leptin or its vehicle-control.


RESULTS
As expected, the hypothermic phenotype of ob/ob mice was partially rescued by administration of leptin at a dose that restores plasma levels into the physiological range. This effect of leptin was not due to increased energy expenditure, as cold exposure markedly and equivalently stimulated energy expenditure and induced activation of brown adipose tissue irrespective of leptin treatment. Instead, the effect of physiological leptin replacement to raise core body temperature of cold-exposed ob/ob mice was associated with reduced thermal conductance, implying a physiological role for leptin in heat conservation. Finally, both leptin- and vehicle-treated ob/ob mice failed to match energy intake to expenditure during cold exposure, resulting in weight loss.


CONCLUSIONS
The physiological effect of leptin to reduce thermal conductance contributes to maintenance of core body temperature under sub-thermoneutral conditions.
Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, 98195, USA.
Karl J
KJ
Kaiyala
UW Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, 98109, USA.
Kayoko
K
Ogimoto
UW Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, 98109, USA.
Jarrell T
JT
Nelson
UW Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, 98109, USA.
Kenjiro
K
Muta
UW Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, 98109, USA. Electronic address: gjmorton@u.washington.edu.
Gregory J
GJ
Morton
BAT, brown adipose tissue; Body temperature; DIO, diet-induced obesity; Energy expenditure; Energy intake; Leptin; Thermal conductance; Thermoregulation; Ucp1, uncoupling protein-1; sc, subcutaneous
Cell Metab. 2009 Feb;9(2):111-2
19187768
Am J Physiol. 1985 May;248(5 Pt 1):E531-9
4039535
Front Physiol. 2013 Mar 14;4:34
23504620
Nature. 1977 Mar 3;266(5597):60-2
840297
Nat Methods. 2011 Dec 28;9(1):57-63
22205519
Endocrinology. 1998 Jan;139(1):8-19
9421392
J Physiol. 1984 May;350:197-207
6747849
Horm Metab Res. 1996 Dec;28(12):659-63
9013737
Science. 1995 Jul 28;269(5223):543-6
7624777
Endocrinology. 1999 Jan;140(1):292-300
9886838
Pflugers Arch. 1978 Feb 22;373(2):189-93
565045
PLoS Genet. 2015 Jun 12;11(6):e1005287
26070086
FASEB J. 2001 Sep;15(11):2048-50
11511509
Br J Nutr. 1979 Nov;42(3):377-85
508700
Cell Metab. 2014 May 6;19(5):741-56
24630813
Biol Bull. 1950 Oct;99(2):237-58
14791422
Comp Biochem Physiol A Mol Integr Physiol. 2011 Mar;158(3):265-75
21134483
Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16241-6
24046370
J Clin Endocrinol Metab. 2002 May;87(5):2391-4
11994393
Anal Bioanal Chem. 2003 Nov;377(6):990-1002
13680051
Fed Proc. 1970 Jul-Aug;29(4):1524-32
5459901
Cell Metab. 2010 Jul 7;12(1):10-7
20620991
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14623-8
10588755
Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E392-401
21062956
Science. 1995 Jul 28;269(5223):540-3
7624776
PLoS One. 2015 Mar 10;10(3):e0119391
25756181
J Nutr. 1980 Jan;110(1):35-41
7354383
Physiol Rev. 2004 Jan;84(1):277-359
14715917
PLoS One. 2012;7(8):e41473
22936977
Physiol Behav. 1990 May;47(5):963-91
2201986
Physiol Behav. 2013 Sep 10;121:49-55
23458626
Metabolism. 1985 Oct;34(10):931-7
4046837
Proc Nutr Soc. 1976 Dec;35(3):133A
1036201
Am J Physiol. 1998 Aug;275(2 Pt 1):E259-64
9688627
Mol Metab. 2015 Mar 10;4(6):461-70
26042200
Diabetologia. 1978 Mar;14(3):141-8
350680
Cell Rep. 2016 Feb 23;14 (7):1621-31
26876182
J Clin Invest. 2000 Jun;105(12):1827-32
10862798
Endocrinology. 2006 May;147(5):2468-80
16469807
J Physiol. 1949 Aug;109(1-2):1-9
15394301
Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E350-7
16595854
Metabolism. 1984 Sep;33(9):853-7
6472117
J Clin Invest. 2005 Dec;115(12):3579-86
16322796
Endocrinology. 2011 Feb;152(2):394-404
21159853
Science. 1995 Jul 28;269(5223):546-9
7624778