Short photoperiod exposure increases adipocyte sensitivity to noradrenergic stimulation in Siberian hamsters

Abstract

Siberian hamsters (Phodopus sungorus) exhibit a naturally occurring, reversible seasonal obesity with body fat peaking in long "summerlike" days (LDs) and reaching a nadir in short "winterlike" days (SDs). These SDinduced decreases in adiposity are mediated largely via sympathetic nervous system (SNS) innervation of white adipose tissue (WAT), as indicated by increased WAT norepinephrine (NE) turnover. We examined whether SDs also increase sensitivity to NE-stimulated lipolysis. This was accomplished by measuring NE-and ␤ 3-adrenoceptor (␤ 3-AR) agonist (BRL-37344)-induced lipolysis (glycerol release) as well as NE-induced cAMP accumulation by inguinal, epididymal, and retroperitoneal WAT (IWAT, EWAT, and RWAT) in isolated adipocytes of LD-and SD-housed hamsters. SDs increased potency/efficacy of NE-triggered lipolysis in a temporally and fat pad-specific manner. Thus when WAT pad mass decreased most rapidly (5 wk of SDs), potency (sensitivity/EC 50) and efficacy (maximal response asymptote) of NE-stimulated lipolysis were increased for all WAT pads and also at 10 wk for IWAT compared with their LD counterparts. SD enhancement of lipolysis was similar for NE and BRL-37344 in IWAT adipocytes. These results, coupled with our previous demonstration that SDs upregulate WAT ␤ 3-AR mRNA expression, suggest that increased ␤ 3-ARs mediated the SD-induced increased NE sensitivity. NE-stimulated adipocyte accumulation of cAMP was greater after 5 wk of SDs for IWAT and EWAT and after 10 wk of SDs for IWAT compared with LDs, with no photoperiod effect for RWAT. Therefore, the SD-induced increase in SNS drive to WAT and increased sensitivity to this drive may work together to increase lipolysis in SDs.lipolysis; body fat; BRL-37344; body weight; sympathetic ENERGY IS PRIMARILY STORED as triacylglycerols in mammals. The vast majority of lipids are located in white adipose tissue (WAT), with considerably lesser amounts stored in brown adipose tissue (BAT) and other organs. WAT functions as a depot for energy storage, whereas BAT can dissipate chemical energy as heat through uncoupling of oxidative phosphorylation from electron transport in its mitochondria (for review see Ref. 8). During positive energy balance, food intake is greater than energy expenditure and lipid is deposited in WAT, whereas during negative energy balance, lipid is mobilized from WAT and transferred to BAT, muscle, and other tissues for oxidation. Chronic positive energy balance generates obesity, a condition that is not readily reversed in most mammals including humans. Obesity typically is associated with serious health risks that include the development of the metabolic syndrome, type II diabetes, and some cancers (35). There are, however, several species of mammals that exhibit seasonal obesity, with increasing adiposity at certain times of the year and decreasing adiposity at other times. Interestingly, although some of these obesities show characteristics similar to those associated with the negative consequences of obesity in humans, we are unaware...

Thematic review series: Adipocyte Biology. Sympathetic and sensory innervation of white adipose tissue

“…78,79), Siberian hamsters respond to SDs with a suite of coordinated sympathetic responses that work together to decrease body fat. Thus, in addition to the SD-induced increase in WAT NETO (26) discussed above, the potency/efficacy of norepinephrine (NE)-triggered lipolysis increases in a temporally and fat pad-specific manner (80). That is, during the rapid decrease in body fat occurring during the first 5-6 weeks of SD exposure, the potency (sensitivity/EC 50 ) and efficacy (maximal response asymptote) of NE-induced lipolysis was increased in isolated adipocytes from IWAT and EWAT compared with isolated adipocytes from their LD counterparts (80).…”

“…Thus, in addition to the SD-induced increase in WAT NETO (26) discussed above, the potency/efficacy of norepinephrine (NE)-triggered lipolysis increases in a temporally and fat pad-specific manner (80). That is, during the rapid decrease in body fat occurring during the first 5-6 weeks of SD exposure, the potency (sensitivity/EC 50 ) and efficacy (maximal response asymptote) of NE-induced lipolysis was increased in isolated adipocytes from IWAT and EWAT compared with isolated adipocytes from their LD counterparts (80). These enhanced responses to NE were most prominent when lipid mobilization was greater (5 vs. 10 weeks of SD exposure) and were more marked in EWAT than in IWAT, paralleling the greater decrease in EWAT than in IWAT mass (80).…”

“…That is, during the rapid decrease in body fat occurring during the first 5-6 weeks of SD exposure, the potency (sensitivity/EC 50 ) and efficacy (maximal response asymptote) of NE-induced lipolysis was increased in isolated adipocytes from IWAT and EWAT compared with isolated adipocytes from their LD counterparts (80). These enhanced responses to NE were most prominent when lipid mobilization was greater (5 vs. 10 weeks of SD exposure) and were more marked in EWAT than in IWAT, paralleling the greater decrease in EWAT than in IWAT mass (80). Moreover, the SD stimulation of lipolysis was similar for NE and BRL 37344 (a specific b 3 -adrenoceptor agonist), implying the primacy of this receptor subtype in this response (80) (see below for a brief discussion of b-and a-adrenoceptors in WAT).…”

An Intact Dorsomedial Hypothalamic Nucleus, but Not the Subzona Incerta or Reuniens Nucleus, Is Necessary for Short-Day Melatonin Signal-Induced Responses in Siberian Hamsters

“…This, in turn, can affect reproductive and other seasonal responses, perhaps including changes in body mass/fat [42] . It is unclear how this system, or whether this system, interacts with the proven MEL receptors colocalized on the SNS outflow neurons to WAT and their clear role in mobilizing lipid stores from these fat pads in SDs [12,13,16] . This possible role of pars tuberalis-hypothalamic T 3 signaling in body mass/fat decreases in SD exposed Siberian hamsters is not without challenge, with no change in thyrotropin-releasing hormone mRNA occurring in SDs [43] .…”

“…Moreover, this initiates lipid mobilization [for reviews, see 14,15 ]. There also are other sympatheticrelated responses that augment the SD-induced increases in SNS drive to WAT to facilitate lipolysis including increased sensitivity to the lipolytic action of norepinephrine [16] , perhaps via SD-triggered increases in the gene expression and subsequent synthesis of the protein for the major adrenergic adipocyte-associated membrane receptor in rodents, the ␤ 3 -adrenoreceptors [16] .…”