Effects of leptin on energy metabolism in β-less mice

Abstract

Objective: To investigate the impact of b-adrenoceptor deficiency on the metabolic effects of leptin. Measurements: Leptin was infused subcutaneously through an osmotic minipump in wild-type (WT) and b 1 /b 2 /b 3 -adrenoceptor knockout (b-less) mice and its effects on food intake, energy expenditure, carbohydrate and lipid utilization as well as on the levels of expression of the brown adipose tissue (BAT), thermogenic marker uncoupling protein-1 (UCP1) and type II deiodinase (D2) mRNAs were compared. Results: Leptin treatment decreased food intake by 23% in both the WT and the b-less mice. In pair-fed animals being used as controls, leptin treatment was found to increase energy expenditure in WT, but not in b-less mice. No difference was observed in carbohydrate or fat utilization between leptin-treated WT and b-less mice. Leptin increased UCP1 and D2 mRNA levels in WT mouse BAT 1.7-and 3-fold, respectively, but had no effect on the expression of these genes in b-less mouse BAT. Conclusion: The stimulatory effects of leptin on oxygen consumption, BAT UCP1 and D2 expression require functional b-adrenoceptors, but its inhibitory effect on food intake and its stimulatory effect on fat utilization is independent of the b-adrenoceptor signalling.

Detection of thermogenesis in rodents in response to anti-obesity drugs and genetic modification

“…It is consistent with the thermogenic effect of leptin on days 2–6 being reduced by about 50% in mice that lack all three β-adrenoceptors (see section Acute Stimulation of Energy Expenditure). However, the same paper reports that leptin did not cause weight loss over 6 days in either wild type or “β-less” mice other than by reducing food intake (Asensio et al, 2008). …”

“…In rats, intracerebroventricular injection of leptin increased body temperature after an hour; peripheral administration took 3 h (Luheshi et al, 1999). Subcutaneous administration has been shown to increase energy expenditure within 12 h in suckling rats (Stehling et al, 1996) and 2 days when infused by minipump in normal mice (Asensio et al, 2008). Leptin increases noradrenaline turnover in brown and white adipose tissue (Collins et al, 1996b) and electrical activity in sympathetic nerves (Dunbar et al, 1997; Hausberg et al, 2002).…”

“…None of this shows whether increased sympathetic activity is responsible for any of the thermogenic activity of leptin, however. Better evidence is that the thermogenic effect on days 2–6 of subcutaneously infused leptin was reduced by about 50% in mice that lack all three β-adrenoceptors (betaless mice) (Asensio et al, 2008). Work in Lep ° b / Lep ° b mice that also lack UCP-1 suggests that elevation of plasma tri-iodothyronine by leptin and activation of sarcoendoplasmic reticulum Ca 2+ ATPase may contribute to some of the remaining thermogenic effect of leptin (Ukropec et al, 2006b).…”

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

“…Leptin treatment was found to increase energy expenditure (oxygen consumption),as well as increased thermogenic marker uncoupling protein-1 and type II deiodinase mRNA levels 1.7-and 3-fold,respectively,in mice [256]. Table 11: Serum proinflammatory cytokines and leptin concentrations in obese children at prepubertal age compared with healthy children of the same age (according to Aygun et al [253] and Kapiotis et al [254]; with own modification).…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…Multiple cytokines and acute inflammation that raise leptin levels may have a potential role also in inflammatory anorexia [641] , especially that leptin treatment increased energy expenditure (oxygen consumption) in animals [656] . It should be noted that in mice with T. gondii infection the dual anorexia and hypermetabolic states were associated with the elevation of TNF-α, IL-1β, IL-2, IL4, IL-5, IL-6, IL-10, and IFN-γ levels [657,658] , and it was reported that various cachectic-anorexic conditions resulted from interactions among cytokines and neurotransmitters as mediators of neurologic and neuropsychiatric manifestations of disease [659,660] .…”