Altered Expression of SOCS3 in the Hypothalamic Arcuate Nucleus during Seasonal Body Mass Changes in the Field Vole, Microtus agrestis

Abstract

We have previously shown that cold-acclimated (8 degrees C) male field voles (Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD, 16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than animals maintained in SD. By infusing voles with exogenous leptin, we have also demonstrated that SD voles respond to the hormone by reducing body mass and food intake, whereas LD animals increasing body mass are resistant to leptin treatment. In the present study, we investigated whether seasonal changes in body mass could be linked to modulation of the leptin signal by suppressor of cytokine signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up to 11 weeks. LD voles increasing body mass had significantly higher levels of SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated changes in expression of NPY, AgRP, POMC and CART genes. These results suggest that voles that regulate body mass at either the lower (SD) or upper (LD) plateau remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a short-term mechanism that enables animals to move between the stable body mass plateaus. Our data provide evidence that expression of SOCS3 in the ARC is involved in the modulation of the strength of the leptin signal to facilitate seasonal cycles in body mass and adiposity.

Lack of leptin activity in blood samples of Adélie penguin and bar-tailed godwit

“…In obese humans, except in extremely rare cases, obesity is associated with decreased sensitivity to leptin and increased circulating leptin levels, a phenomenon that has been termed leptin resistance (Frederich et al 1995, Caro et al 1996, Ur et al 1996, Montez et al 2005. Leptin resistance can be either a pathological state, for example, in diet-induced obesity or an adaptive response allowing shifts in body-energy stores, similar to that occurring in seasonal breeders (Rousseau et al 2002, Tups et al 2004, Krol et al 2007, Zieba et al 2008, Scarpace & Zhang 2009, Tups 2009). For example, the Siberian hamster, which has been intensively studied as a model of seasonal mammals, spontaneously reduces its BW by w40% over a 12-week period in winter (Heldmaier et al 1982).…”

Leptin resistance: a prediposing factor for diet-induced obesity

“…There are several models of naturally occurring, programmed leptin resistance, including that displayed in seasonal animals (27,28,63) or during pregnancy/lactation (2,21), where increased food consumption and weight gain are necessary to meet the particular biological demands. Additionally, several genetic models of obesity associated with defective or absent leptin receptors reflect a tachyphylaxis to leptin responses (17).…”

Seasonal effects of central leptin infusion and prolactin treatment on pituitary SOCS-3 gene expression in ewes

“…Studies carried out on field vole (Microtus agrestis), a seasonal animal, provide very interesting information. Field voles, similar to Siberian hamsters, exhibit annual fluctuations in BW during the year and reduction in leptin resistance during LD (Krol et al 2007). This paper raised the very important question of whether the increased level of expression of SOCS-3 is the result or the cause of concomitant weight gain.…”

“…This paper raised the very important question of whether the increased level of expression of SOCS-3 is the result or the cause of concomitant weight gain. Furthermore, authors suggested that melatonin, by way of direct or indirect interaction, may be responsible for seasonal changes in the expression of SOCS-3 in the hypothalamus (Krol et al 2007). Since melatonin is the main molecule responsible for signalling the changes in the length of the day, this pineal hormone and/or other hormones that have concentrations in the bloodstream that are highly dependent on the concentration of melatonin (e.g.…”