Photoperiodic Regulation of Leptin Resistance in the Seasonally Breeding Siberian Hamster ( Phodopus sungorus )

Adult mammals are typically highly resistant to perturbations in their energy balance. In obese humans, however, this control appears to be lost. Apart from a few exceptional cases, this loss of control occurs despite appropriate levels of circulating leptin -suggesting that elevated adiposity may be a consequence of failure to respond to the leptin signal: leptin resistance. When cold-acclimated male field voles (Microtus agrestis) are transferred from short (SD, 8 h light) to long (LD, 16 h light) photoperiods, they increase dramatically in body mass and fatness for about 4 weeks. After this period, their mass stabilizes at a new plateau about 25% higher than animals maintained in SD. The increase in adiposity is not caused by significant increases in food intake, but reflects an increase in digestive efficiency. Measures of circulating leptin reveal that the increased adiposity is matched by increased circulating leptin. By infusing voles with exogenous leptin, we have demonstrated that SD voles are leptin sensitive (reducing both body mass and food intake), whereas LD animals are leptin resistant. Voles may therefore be a useful model for understanding the process of leptin resistance. The change in leptin sensitivity in voles was not associated with changes in the levels of gene expression of the orexogenic or anorexogenic neuropeptides, such as neuropeptide Y, agouti-related peptide, POMC and cocaine-and amphetamine-regulated transcript, measured in the hypothalamic arcuate nucleus (ARC). During the phase that body mass was increasing, however, there was a transient increase in the ARC expression of suppressor of cytokine signalling-3 (SOCS3). These data suggest that the changes in the expression of SOCS3 in the ARC may be involved in leptin resistance. However, the mechanism by which these changes may be linked to alterations in digestive efficiency that underpin the changes in adiposity, or how the differences are signalled by changes in photoperiod, remains unclear.

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Regulation of body mass and adiposity in the field vole, Microtus agrestis: a model of leptin resistance

Król¹,

Speakman²

2007

“…We have shown elsewhere that longday housed hamsters are refractory to these leptin infusion protocols and do not exhibit any significant feeding, reproductive or weight-loss response (Atcha et al 2000). We have proposed that this resistance to leptin may be mediated at the level of the CNS (Rousseau et al 2002). Here, our data clearly show that LD-housed animals do not respond to leptin in terms of any of the skeletal parameters measured.…”

Section: Discussionmentioning

confidence: 46%

“…Pumps were replaced after 7 days for a further 1-week period. On Day 14 of treatment, a single blood sample was taken from each hamster under halothane anaesthesia by cardiac puncture for serum leptin determinations as previously described (Rousseau et al 2002). Animals were then killed by cervical dislocation and the abdominal fat pads dissected and weighed.…”

Section: Experimental Protocolsmentioning

confidence: 99%

Skeletal bone morphology is resistant to the high amplitude seasonal leptin cycle in the Siberian hamster

Rousseau

Atcha²,

Denton³

et al. 2005

Recent studies have suggested that the adipocyte-derived hormone, leptin, plays a role in the regulation of metabolism. Here, we tested this hypothesis in the seasonally breeding Siberian hamster, as this species exhibits profound seasonal changes in adiposity and circulating leptin concentrations driven by the annual photoperiodic cycle. Male hamsters were kept in either long (LD) or short (SD) photoperiods. Following exposure to short photoperiods for 8 weeks animals exhibited a significant weight-loss and a 16-fold reduction of serum leptin concentrations. At Week 9, animals in both photoperiods were infused with leptin or PBS via osmotic mini-pump for 14 days. Chronic leptin infusion mimicked LD-like concentrations in SDhoused animals and caused a further decline in body weight and adipose tissue. In LD-housed animals, leptin infusion resulted in a significant elevation of serum concentrations above natural LD-like levels, but had no discernable effect on body weight or overall adiposity. Both bending and compression characteristics and histomorphometric measurements of trabecular bone mass were unaltered by leptin treatment or photoperiod. Our data therefore show that despite a high natural amplitude cycle of leptin, this hormone has no apparent role in the regulation of bone metabolism, and therefore do not support recent propositions that this hormone is an important component in the metabolism of bone tissue.

“…If a hormone is no longer secreted in pulses, the target tissue will become desensitized from maintaining a steadystate level (Baulieu 1990). Seasonal photoperiod changes have been shown by Rousseau et al (2002) in Siberian hamsters to modulate the sensitivity to leptin. Horses exhibit seasonal variations of leptin, which has been reported to decrease as they transition from summer into autumn and winter without subsequent weight loss (Gentry et al 2002, Buff et al 2005.…”

Section: Discussionmentioning

confidence: 99%

Induction of pulsatile secretion of leptin in horses following thyroidectomy

Buff

Messer²,

Cogswell³

et al. 2007

Endocrine characteristics of Quarter Horse-type mares were determined during a 68 h feed deprivation and again in the same mares following surgical thyroidectomy (THX). A crossover experimental design was implemented, in which mares received brome hay available ad libitum (FED) or were food deprived (RES) for 68 h. Blood samples were collected every 20 min for 48 h, beginning 20 h after the onset of food deprivation. Concentrations of triiodothyronine and thyroxine were undetectable post-THX. Plasma concentrations of thyrotropin were greater post-THX versus pre-THX (P!0 . 001). Plasma concentrations of leptin were greater in the THX FED group than in the THX RES group (P! 0 . 01). The existence of leptin pulse secretion was found only in post-THX compared with the same horses pre-THX (PZ 0 . 02). We theorize that non-pulsatile secretion of leptin may have contributed to the survival of this species, as it evolved in the regions of seasonal availability of food. Lack of pulsatile secretion of leptin may contribute to the accumulation of energy stores by modulating leptin sensitivity.