Temperature Dependence of O₂ Consumption; Opposite Effects of Leptin and Etomoxir on Respiratory Quotient in Mice

Abstract

HÖ GBERG, HELENA, LARS ENGBLOM, ÅSA EKDAHL, VERONICA LIDELL, ERIK WALUM, AND PE TERIS ALBERTS. Temperature dependence of O 2 consumption; opposite effects of leptin and etomoxir on respiratory quotient in mice. Obesity. 2006;14:673-682. Objectives: The aims were to compare the temperature dependence of the metabolic rate in young ob/ob mice with that in mature ob/ob and db/db mice and to examine the effect on the metabolic substrate preference of leptin and etomoxir in ob/ob, C57BL/6J (wild-type), and db/db mice. Research Methods and Procedures:In vivo oxygen consumption and carbon dioxide production were continuously measured by indirect calorimetry, and body temperature and total locomotor activity were measured by an implanted transponder. Leptin, etomoxir, or vehicle was administered intraperitoneally. Results: The temperature dependence of the metabolic rate of mature ob/ob and db/db mice were similar to that in wild-type mice. In young 6-week-old ob/ob mice, the metabolic rate was almost doubled at 15°C. Leptin (2 ϫ 3 mg/kg) decreased the respiratory quotient (RQ) and carbon dioxide production but did not alter oxygen consumption, body temperature, or locomotor activity in ob/ob and C57BL/6J mice and had no effect in the db/db mice. Etomoxir (2 ϫ 30 mg/kg) enhanced RQ and decreased oxygen consumption, carbon dioxide production, and body temperature in ob/ob, C57BL/6J, and db/db mice. Total locomotor activity was reduced in ob/ob and C57BL/6J mice. Discussion: In young ob/ob mice, the temperature sensitivity was enhanced compared with mature mice. Leptin and etomoxir had opposite effects on metabolic substrate preference. Leptin and lowered environmental temperature increased the relative fat oxidation as indicated by decreased RQ, possibly through activation of the sympathetic nervous system.

CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor

“…Thus, the low levels of circulating leptin in Clic5 Ϫ/Ϫ mice likely contribute to their increased susceptibility to torpor. In studies utilizing indirect calorimetry, treatment of leptin-deficient (ob/ ob) mice with leptin led to a decrease in RQ but had no effect on RQ in mice lacking the leptin receptor, suggesting that leptin stimulates fat metabolism (27). In our own studies, RQ was greater in Clic5 Ϫ/Ϫ mice than in wild-type controls (Fig.…”

Adipose tissue in control of metabolism

“…However, some groups found that leptin administration has little effect on the energy expenditure without normalization (Ukropec et al 2006, Fischer et al 2016. Moreover, other two studies show that leptin treatment has little effect on energy expenditure even when the data is normalized with body mass (Doring et al 1998, Hogberg et al 2006. This controversy needs to be further clarified.…”

Neuroregulation of nonexercise activity thermogenesis and obesity resistance

“…Likely the most consistent data among this group is for leptin. This adiposity-signaling hormone increased spontaneous physical activity and energy expenditure in obese, ob/ob, and C57BL/6J mice (84,60,113). Transgenic mice with disrupted leptin receptor signaling show reduced spontaneous physical activity (7), while restoring hypothalamic arcuate nucleus leptin receptor STAT3 signaling normalized spontaneous physical activity (29).…”