Leptin Signaling Is Required for Adaptive Changes in Food Intake, but Not Energy Expenditure, in Response to Different Thermal Conditions

Abstract

Survival of free-living animals depends on the ability to maintain core body temperature in the face of rapid and dramatic changes in their thermal environment. If food intake is not adjusted to meet the changing energy demands associated with changes of ambient temperature, a serious challenge to body energy stores can occur. To more fully understand the coupling of thermoregulation to energy homeostasis in normal animals and to investigate the role of the adipose hormone leptin to this process, comprehensive measures of energy homeostasis and core temperature were obtained in leptin-deficient ob/ob mice and their wild-type (WT) littermate controls when housed under cool (14°C), usual (22°C) or ∼ thermoneutral (30°C) conditions. Our findings extend previous evidence that WT mice robustly defend normothermia in response to either a lowering (14°C) or an increase (30°C) of ambient temperature without changes in body weight or body composition. In contrast, leptin-deficient, ob/ob mice fail to defend normothermia at ambient temperatures lower than thermoneutrality and exhibit marked losses of both body fat and lean mass when exposed to cooler environments (14°C). Our findings further demonstrate a strong inverse relationship between ambient temperature and energy expenditure in WT mice, a relationship that is preserved in ob/ob mice. However, thermal conductance analysis indicates defective heat retention in ob/ob mice, irrespective of temperature. While a negative relationship between ambient temperature and energy intake also exists in WT mice, this relationship is disrupted in ob/ob mice. Thus, to meet the thermoregulatory demands of different ambient temperatures, leptin signaling is required for adaptive changes in both energy intake and thermal conductance. A better understanding of the mechanisms coupling thermoregulation to energy homeostasis may lead to the development of new approaches for the treatment of obesity.

No insulating effect of obesity

“…Similarly to the case in DIO mice (Figs. 3 and 6), and as pointed out earlier (21,31), the total metabolic rates of ob/ob mice were higher than in the wild-type mice during the entire Scholander experiment (Fig. 7A).…”

Adipose tissue in control of metabolism

“…However, some of later studies do not support this and argue that the hypometabolism in leptin-deficient mice is only the effect of normalization (Himms-Hagen 1997, Kaiyala et al 2015, Fischer et al 2016. When the energy expenditure is not normalized, leptin deficiency leads to increase of oxygen consumption and hyper-metabolism (Himms-Hagen 1997, Kaiyala et al 2015).…”

Revisiting How the Brain Senses Glucose—And Why

“…Owing to the high fidelity of this system, normal mice placed into a cold environment are able to profoundly increase heat production and reduce heat dissipation, despite virtually no detectable change in average core temperature (Kaiyala et al, 2015). This impressive feat would not be possible if temperature sensing were performed primarily by neurons in the brain, since the brain temperature would have to change before a homeostatic response could be engaged.…”