Contrasting Effects of Leptin on Food Anticipatory and Total Locomotor Activity

Abstract

Obese, leptin deficient obob mice have profoundly decreased activity and increased food seeking behavior. The decreased activity has been attributed to obesity. In mice, we tested the hypothesis that leptin increases total locomotor activity but inhibits food anticipatory activity. We also sought to determine if leptin induced increases in total locomotor activity are independent of changes in body weight and obesity. We studied obob mice and also created a novel transgenic mouse where leptin is over-expressed in a tetracycline-off system and can be abruptly and non-invasively suppressed by doxycycline within few hours. The studies were performed using two independent behavioral assays: home cage activity (HCA) and running wheel activity (RWA). Systemic administration of leptin (150 ng/hr) to obob mice produced a 122%±30% (mean ± SEM) increase (p≤0.01) in locomotor activity within 2 days In addition, cerebroventricular administration of leptin (5 ng/hr) also produced an early and progressive increase in total locomotor activity beginning on the 1st day (+28±8%; p≤0.05) and increasing to +69±23% on day 3 without a decrease in body weight during this time. The increase in activity was restricted to the dark phase. Conversely, in a tet-off transgenic obob mouse line, acute leptin suppression reduced spontaneous locomotor activity. To further define activities that are leptin regulated, we assayed food anticipatory activity (FAA) and found that it was markedly augmented in obob mice compared to wild type mice (+38±6.7 in obob vs +20±6.3% in wild type at peak; mean ± SEM; p≤0.001) and abolished by leptin. Although melanocortin-3 receptors (MC3R) reportedly mediate FAA, we found augmented FAA and preserved inhibitory effects of leptin on FAA in MC3R−/−obob mice. In summary, this study demonstrates that total activity and FAA are regulated independently by leptin. Leptin, acting in the central nervous system and at physiologic levels, produces early increases in locomotor activity before substantial weight loss. In contrast, leptin suppresses augmented food anticipatory activity in obob mice.

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

“…Leptin, an adipocyte-derived hormone, is a long-term regulator of body weight, acting through inhibition of food intake and stimulation of both energy expenditure (37) and locomotor activity (38).…”

Endocrine regulation of circadian physiology

“…Although the anatomical and molecular makeup of this food-entrainable oscillator (FEO) underlying FAA rhythms is still largely unknown, both leptin and ghrelin have been shown to play a role in regulating FAA rhythms. ob/ob mice and Obrbmutant Zucker rats show increased FAA under RF, which can be suppressed by the administration of recombinant leptin (Mistlberger & Marchant 1999, Ribeiro et al 2011. In contrast, ghrelin receptor (Ghsr)-deficient mice show impaired FAA (Blum et al 2009, LeSauter et al 2009, Lamont et al 2014; though intriguingly, ghrelin-deficient mice are normal under these conditions (Szentirmai et al 2010).…”

Zaburzenia funkcji tarczycy u dzieci z otyłością i nadwagą

“…Serum leptin levels are proportional to the body's adiposity [8]. Leptin regulates body weight through inhibition of food intake and stimulation of energy expenditure and locomotor activity [8,30,35]. The concentrations of leptin transmit information about the amount of fat to the central nervous system, which leads to a decrease in appetite and food intake [36].…”