Effects of glucocorticoids on energy metabolism and food intake in humans

Abstract

The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite.

Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis

“…(Dagogo-Jack et al, 1997;Miell et al, 1996;Newcomer et al, 1998;Slieker et al, 1996;York, 1996) CRH and Ucn 3 (Bernier, 2006;Ohata and Shibasaki, 2011;Smagin et al, 1998) CART (Kask et al, 2000;Xu et al, 2010) Nesfatin-1 (Goebel et al, 2009;Stengel et al, 2011) NPW (Beck et al, 2010) Melanocortins (Liu et al, 2007;Yamano et al, 2004) central monoaminergic systems (Gibson, 2006) autonomous nervous system (Seematter et al, 2004) Stress induces hyperphagia due to reduction of: sensor specific satiety (Ahn and Phillips, 2012;Ortolani et al, 2011) stressor aversiveness (Piazza and Le Moal, 1997) CRH signaling? (Foster et al, 2009;la Fleur et al, 2005;Pecoraro et al, 2004) due to activation of central reward pathways (Piazza and Le Moal, 1997), due to alterations in gut microbiota (Tehrani et al, 2012) Glucocorticoids induce hyperphagia (Dallman, 1993;Drapeau et al, 2003;Epel et al, 2000;Tataranni et al, 1996) due to increased signaling of: NPY (Gyengesi et al, 2010;Krysiak et al, 1999;McKibbin et al, 1992;White et al, 1994;Wilding et al, 1993), AgRP (Coll et al, 2005;Savontaus et al, 2002), Nociceptin (Green and Devine, 2009;Nativio et al, 2011;…”

“…Appetite in humans and animals follows changes in adrenal steroid levels. Anorexia and weight loss are hallmarks of adrenal insufficiency in Addison's disease, whereas increased appetite correlates with GC overproduction in Cushing's syndrome and with exogenous GC administration in normal volunteers (Tataranni et al, 1996). In women experimental stressinduced cortisol secretion increased appetite and craving for sugar (Epel et al, 2000).…”

AMPK as a mediator of hormonal signalling

“…We have suggested that AMPK is involved in the central and peripheral effects of glucocorticoids. Glucocorticoids activate hypothalamic AMPK activity in vivo (Christ-Crain et al 2008) either directly or via stimulation of endocannabinoid synthesis (Di et al 2005, Christ-Crain et al 2008, and these effects could lead to appetite stimulation (Tataranni et al 1996). In the periphery, glucocorticoids inhibit AMPK activity in adipose tissue, leading to increased lipogenesis and fat storage (Christ-Crain et al 2008).…”

Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats

“…GCTC-induced insulin resistance results in decreased insulin-stimulated glucose uptake in muscle [6], and increased plasma concentrations of NEFA, insulin and leptin [7,8], with troglitazone antagonising this effect [7]. At the whole body level, increased GCTC concentrations are known to increase oxygen consumption [9][10][11], and decrease food intake [12,13] resulting in a more negative energy balance than in pair-fed animals. We have shown that there is a decreased efficiency of oxidative phosphorylation in the liver mitochondria of dexamethasone treated rats [13].…”