Protective effects of leptin in body weight regulation do not involve an increase in thermogenesis/energy expenditure

Protective effects of leptin in body weight regulation do not involve an increase in thermogenesis/energy expenditure

A large number of physiological effects are attributed to leptin. Particularly, there is a general notion that leptin reduces body weight through both a reduction of food intake and an increase in thermogenesis/ energy expenditure (EE).

Whereas a multitude of investigations have, over the years, detailed the pathways involved in the hypophagic effect of leptin, only a few studies have addressed the suggested thermogenic pathway. That leptin should be thermogenic is based, e.g., on observations that the absence of leptin (as in the ob/ob mice) has been associated with hypometabolism and hypothermia and with brown adipose tissue (BAT) inactivation.

Accordingly, one effect of leptin would be to induce thermogenesis by the activation of BAT and, through this, to counteract hypothermia and promote body weight loss

In contrast to these established views, researchers found that BAT is fully functional and that leptin treatment did not increase thermogenesis in wild-type or in ob/ob mice. Rather, ob/ob mice showed a decreased but defended body temperature (i.e., were anapyrexic, not hypothermic) that was normalized to wild-type levels after leptin treatment.

This was not accompanied by increased energy expenditure or BAT recruitment but, instead, was mediated by decreased tail heat loss.

The weight-reducing hypophagic effects of leptin are, therefore, not augmented through a thermogenic effect of leptin; leptin is, however, pyrexic, i.e., it alters centrally regulated thresholds of thermoregulatory mechanisms, in parallel to effects of other cytokines.

http://www.cell.com/cell-reports/abstract/S2211-1247(16)30019-5

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