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 SD-induced 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 β3-adrenoceptor (β3-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/EC50) 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 β3-AR mRNA expression, suggest that increased β3-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.
- body fat
- body weight
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 of any data showing they have adverse health consequences in these species.
One species that exhibits a naturally occurring, reversible seasonal obesity is the Siberian hamster (Phodopus sungorus; for review see Ref. 4). Specifically, Siberian hamsters become naturally obese during the first 2–3 mo of life when raised in long “summerlike” days (LDs) and became thinner when exposed to short “winterlike” days (SDs), the latter occurring without an initial decrease in food intake (Ref. 37). These body fat changes, as well as other seasonal responses, are triggered by daylength-induced changes in the nocturnal duration of secretion of the pineal hormone melatonin (for reviews see Ref. 6). At a systems level, the likely means by which melatonin triggers the body fat loss is via activation of the sympathetic nervous system (SNS) outflow from brain to WAT (2). These outflow neurons express mRNA for the functional melatonin receptor (MEL1a), and their stimulation appears to ultimately result in increases in WAT lipid mobilization through increased sympathetic drive (36). Support for this scenario comes from the now overwhelming neuroanatomical, neurochemical, and functional evidence for the SNS innervation of WAT and its role as the principal means of initiating lipolysis (for review see Ref. 3). That is, the release of the predominant sympathetic postganglionic neurotransmitter norepinephrine (NE) and its stimulation of membrane-bound adipocyte β-adrenoceptors is thought to be the underlying mechanism for lipolysis in WAT. The postganglionic innervation of epididymal and inguinal WAT (EWAT and IWAT, respectively) has been demonstrated bidirectionally using fluorescent retrograde and anterograde tract tracers in Siberian hamsters (40). In addition, the SNS outflow from the brain to EWAT, IWAT, and retroperitoneal WAT (RWAT) has been defined using a transneuronal tract tracer, the pseudorabies virus (2, 7, 36). Moreover, this SD-induced increase in WAT lipid mobilization is greater and occurs earlier from more internally located fat pads (e.g., EWAT and RWAT) compared with more externally located depots (e.g., IWAT; Refs. 5, 37), as well as having the expected corresponding greater and earlier increases in sympathetic drive, as assessed by NE turnover (40). Finally, these SD-induced increases in WAT lipid mobilization are largely blocked by local surgical or chemical denervation of WAT (16, 41) and are blocked more fully with the addition of adrenal demedullation (16), further attesting to the pivotal role of the SNS innervation of WAT in the reversibility of this seasonal obesity.
In addition to these SD-induced increases in SNS drive to WAT, there also could be changes in β-adrenoceptor function that could augment the increased sympathetic drive to this tissue. That is, a combination of increased sensitivity to catecholamines in the periphery with the centrally mediated increase in SNS outflow to WAT would enhance the SD-induced lipid mobilization. An analogous combination occurs in BAT, where increases in SNS drive are associated with increases in thermogenic capacity (32), as evidenced by increases in mitochondrial number (24) and uncoupling protein-1 (UCP-1) gene expression (17) in this species. In our model of reversible seasonal obesity, SD-exposed Siberian hamsters have increases in WAT β3-adrenergic receptor (β3-AR) mRNA levels (17). It is unknown, however, whether these increases in β3-AR mRNA levels are translated into enhanced functional differences in lipolytic responsiveness to noradrenergic stimulation. That is, increases in β3-AR mRNA levels may not be reflected in increases in receptor number, or the SD-associated increases in SNS drive to WAT could negate any increases in receptor number via post-receptor desensitization (11). Alternatively, if increases in β3-AR mRNA are translated into increases in β3-ARs, then increases in signaling through the cAMP/protein kinase A/hormone-sensitive lipase (HSL) pathway could result in more efficient lipolysis in the absence of a counterregulatory negative regulation of cAMP (e.g., increased phosphodiesterase activity). Specifically, small increases in functional β3-ARs would first be expected to increase the efficacy (asymptote of the maximal response to NE), rather than the potency (sensitivity or −log EC50) of NE, whereas large increases in β3-ARs likely would affect both potency and efficacy. An analogous situation occurs in mice, in which the increase in β3-AR expression that occurs after weaning increases the responsiveness of adipocytes to β-adrenergic stimulation (21). Any or all of these possibilities could significantly contribute to the SD-induced increase in lipid mobilization beyond that which would be produced by the already documented SD-induced increase in SNS drive to WAT (40).
Therefore, the purpose of the present study was to test whether changes in adipocyte responsiveness to NE are associated with the SD-induced increases in lipid mobilization from Siberian hamsters WAT. This was accomplished by isolating adipocytes from IWAT, EWAT, and RWAT of Siberian hamsters housed in LDs, or transferred from LDs to SDs, and measuring lipolysis through glycerol release in response to NE as well as the specific β3-AR agonist BRL-37344 (26) in IWAT adipocytes. In addition, we examined an early step in the signaling pathway that would reflect changes in receptor density: cAMP accumulation in response to NE.
Animals and initial housing conditions.
Male Siberian hamsters were raised in our breeding colony and housed in a LD photoperiod (16:8-h light-dark cycle with lights on at 0300 EST). These animals were weaned at 21 day of age and housed with same-sex siblings in groups of 8–12 hamsters in polyvinyl cages (48 × 27 × 15 cm) with corncob bedding and nestlets until used in the present experiment at ∼3 mo of age. Hamsters (n = 60) were then housed individually in polypropylene cages (27.8 × 7.5 × 13.0 cm) in the LD photoperiod. Room temperature was kept constant at 20°C, and relative humidity was maintained at 50 ± 5% throughout the experiment. All animals had ad libitum access to Purina rodent diet (Rat Chow 5001; St. Louis, MO) and tap water. All experimental procedures were approved by the Georgia State University Institutional Animal Care and Use Committee in accordance with Public Health Service and United States Department of Agriculture guidelines.
After 2 wk of acclimation to single housing, hamsters were divided into four experimental groups balanced for body mass change and absolute body mass measured during this acclimation period. Two groups remained in LDs, and two groups were transferred to SDs (8:16-h light-dark cycle with lights on at 0300) for 5 or 10 wk. SD-housed hamsters and their LD-housed counterparts were killed after 5 wk of SD exposure, the period when body and lipid mass decreases most rapidly and independently of food intake (37), or after 10 wk of SD exposure, the period when body and lipid mass become asymptotic and that is associated with a significant decrease in food intake (37). Hamsters were killed with an overdose of pentobarbital sodium (70 mg/kg), IWAT, EWAT, and RWAT were harvested and weighed, and adipocytes were isolated as described in Adipocyte isolation and incubation. Testes were harvested to obtain an estimate of reproductive status and a body fat-independent measure of the response to SDs. That is, SD-housed animals regress their testes, and hamsters with testes of <300 mg have nearly undetectable circulating concentrations of testosterone (31); therefore, only data from SD hamsters achieving this criterion were analyzed.
Because of the time required to harvest, isolate, and test the isolated adipocytes while fresh, as well as because of the low yield of adipocytes from these small WAT pads, each experimental group was divided into three subgroups matched for body mass change and absolute body mass with the remaining animals from their respective groups. The animals in each subgroup were food deprived for 2 h and then killed on successive days at the start of the 5- and 10-wk time points. Isolated adipocytes from these animals were utilized to evaluate 1) glycerol release in response to NE and BRL-37344 in adipocytes isolated from IWAT, 2) glycerol release in response to NE in adipocytes isolated from EWAT and RWAT, and 3) steady-state cAMP levels in response to NE in adipocytes isolated from IWAT, EWAT, and RWAT. Because there were no significant differences in the terminal measures of body mass/body mass change or testes and WAT masses among these subgroups within their respective photoperiod-time point group, their data were combined into one group for each condition.
Adipocyte isolation and incubation.
In vitro lipolysis (glycerol release) measures were performed essentially as described by Dark et al. (15). Briefly, harvested WAT destined for adipocyte isolation was immediately rinsed with warm 0.15 mM NaCl and adipocytes were isolated in warm Krebs-Ringer buffer with 10 mM HEPES, 5.5 mM glucose and 4% fatty acid-free bovine serum albumin, pH 7.4, via collagenase digestion (1.7 mg/ml collagenase) according to the method of Rodbell (34). Thereafter, adipocytes were washed three times with Krebs-Ringer-HEPES and resuspended to a final concentration of ∼40,000 cells/ml. Aliquots (1 ml) were incubated with or without the test chemicals for 1.5 h in a 37°C water bath with gentle shaking. To clamp basal lipolysis at low reproducible levels, all incubations contained adenosine deaminase (ADA; 4 μg/ml) to remove endogenous adenosine and the bioactive nonhydrolyzable adenosine analog phenylisopropyl adenosine (PIA; 100 nM) (25). Tubes were inserted in ice to stop the reactions.
WAT cellularity measurements.
To express glycerol release in terms of fat cell number (18), we determined the number of fat cells in the 1-ml aliquots by performing Coulter Counter analysis (Beckman Coulter, Fullerton, CA) using fresh, unfixed adipocytes (30).
Glycerol release assay.
For glycerol release assays, Siberian hamsters exposed to SDs for 5 or 10 wk and their LD-housed counterparts (n = 6–10 hamsters/group) were killed, and their IWAT, EWAT, and RWAT adipocytes were isolated and incubated with NE (10−5, 10−6,10−7, 10−8, or 10−9 M) and, for IWAT only, with BRL-37344 (10−6,10−7, 10−8, 10−9, 10−10, or 10−11 M). Lipolytic rates were calculated by measuring the net glycerol release into the incubation medium. Glycerol was measured in deproteinized, neutralized medium extracts (29) according to the enzymatic method of Laurell and Tibbling (28). Concentration-response curves were generated for each WAT depot at both time points. The curves were constructed by plotting the relative increase in glycerol release above basal levels vs. the log of the molar NE or BRL-37344 concentration according to convention (9).
cAMP accumulation assay.
Adipocytes were isolated and incubated as described, and the incubations were stopped after 10 min by placing the tubes on ice. The samples were homogenized and cellular debris was precipitated by adding 50 μl of ice-cold 50% trichloroacetic acid to 950 μl of the cell suspension and centrifuging at 4°C. The cAMP in the supernatant was measured as described by Gettys et al. (20) according to the general method of Harper and Brooker (22), using polyclonal antisera produced by Gettys et al. (19). Concentration-response curves were generated for each WAT depot at both time points by plotting the relative increase in cAMP over basal levels vs. the log of the molar NE concentration.
Body and tissue mass comparisons were made by one-way analyses of variance (SigmaStat v2.0; Jandel Scientific, San Rafael, CA). Post hoc differences between means were determined using Tukey's honestly significant difference tests as appropriate (SigmaStat v2.0). Agonist-induced stimulation of glycerol release and cAMP accumulation were characterized essentially as previously described (21). Least-squares analysis was used to fit curves to the observations, and F-tests were used to determine whether the data were best represented by separate curves (Prism 4.0; GraphPad Software, San Diego, CA). Estimates of the concentration of agonist producing half-maximal response (potency/sensitivity, or −log EC50) and maximal responses (efficacy, or the estimate of the asymptote of the maximal response) were obtained using an iterative nonlinear least-squares routine. Confidence intervals (95%) were constructed to test for differences between experimental groups in agonist potency and efficacy (Prism 4.0). For all tests, differences among means were considered significant if P < 0.05. Exact probabilities and test values have been omitted for simplification and clarity of presentation of the results.
Body and adipose depot masses decreased after short photoperiod exposure.
Animals maintained in short days for either 5 or 10 wk (SD-5 and SD-10, respectively) weighed significantly less than LD animals (P < 0.05; Fig. 1). Mean paired testes mass was significantly reduced in SD-5 and SD-10 hamsters (means ± SE: 0.098 ± 0.011 and 0.085 ± 0.009 g, respectively) compared with their LD-5 and LD-10 counterparts (means ± SE: 0.933 ± 0.026 and 0.908 ± 0.034 g, respectively; P values <0.05). IWAT, EWAT, and RWAT masses were significantly smaller in SD-5 and SD-10 hamsters compared with their LD counterparts (P values <0.05; Fig. 2). There were no significant differences in WAT mass between experimental groups within a photoperiod.
NE-sensitivity is increased by short photoperiod exposure.
Exposure to SD for 5 or 10 wk significantly increased the sensitivity of IWAT adipocytes to NE (P values <0.05; Fig. 3, A and B, respectively) and to the specific β3-AR agonist BRL-37344 (P values <0.05; Fig. 3, C and D, respectively) compared with LDs. More specifically, both the potency (sensitivity, or −log EC50) and efficacy (estimate of the asymptote of maximal response) of NE was significantly increased in SDs for both time points (Fig. 3). Both NE potency and efficacy also were significantly increased in EWAT and RWAT adipocytes from SD-5 hamsters (P values <0.05; Fig. 4, A and C, respectively) compared with LD-5, but in SD-10 and LD-10 hamsters, NE sensitivity was greater in the LD group (Fig. 4, B and D).
NE-stimulated cAMP accumulation is generally increased in SDs.
NE (10 μM)-stimulated cAMP accumulation by IWAT and EWAT was significantly greater in SD-5 hamsters compared with their LD controls (P values <0.05; Table 1). After 10 wk of SD exposure, however, only NE-stimulated cAMP accumulation in IWAT was significantly greater than in LDs (P < 0.05; Table 1). NE-stimulated cAMP accumulation in adipocytes isolated from RWAT was not affected by the photoperiod (Table 1).
The rate of lipid mobilization from WAT depots is most rapid during the first 5–6 wk of SD exposure in Siberian hamsters (37), and, moreover, there is a greater lipid loss from visceral (RWAT and EWAT) vs. subcutaneous (IWAT and dorsosubcutaneous WAT) depots (5). The principal mechanism underlying both the general decrease in adiposity and the fat pad-specific greater decrease in visceral WAT mass is a parallel SD-induced increase in sympathetic drive (NE turnover; Ref. 40) to this tissue. Similarly, with prolonged SD exposure (approximately >10 wk; Ref. 40), the diminishing visceral and persisting subcutaneous WAT lipid mobilization also is associated with corresponding changes in sympathetic drive to these WAT depots (40). The results of the present study, however, demonstrate that in addition to these changes in WAT sympathetic drive, SDs increased the sensitivity to noradrenergic stimulation of glycerol release (lipolysis) in isolated WAT adipocytes. Specifically, both the efficacy and potency of NE-triggered glycerol release was increased in adipocytes from all WAT pads early after 5 wk of SD exposure and, in addition, in IWAT adipocytes after 10 wk of SD exposure. Moreover, the β3-AR-selective agonist BRL-37344 produced an enhancement of glycerol release similar to that caused by NE from IWAT adipocytes, suggesting the involvement of this adrenoceptor subtype in this lipid mobilization. A previous demonstration from our laboratory (17) showing that SDs trigger increases in β3-AR mRNA in WAT provides a possible explanation for the SD-induced increased efficacy and potency to these noradrenergic stimuli. The lack of an increased potency of the lipolytic effect of NE at 10 wk in visceral fat (EWAT and RWAT) also nicely parallels the decreased sympathetic drive (NE turnover) in these pads at this time compared with LDs as well as to SDs at 5 wk (40). Finally, SDs also increased WAT adipocyte cAMP accumulation in IWAT and EWAT after 5 wk and in IWAT at 10 wk in accordance with the glycerol release data, whereas this SD effect was not exhibited by RWAT. Thus SD exposure causes increases in sympathetic drive to WAT (40) and produces a corresponding enhancement of potency and efficacy to NE in a temporally and fat pad-specific manner.
The present results largely contradict those of a previous study by Atgie et al. (1), who found no SD enhancement of NE-induced lipolysis by adipocytes isolated from Siberian hamster WAT. There are, however, two key and critical differences between these studies that likely explain these discrepant results. First, in the present study, lipolysis was examined separately in the three WAT depots (IWAT, EWAT, and RWAT), whereas lipolysis in the previous study (1) was tested from adipocytes that were pooled from these three depots as well as from the perirenal WAT depot. Consequently, the depot-specific differences in noradrenergic responsiveness and potency observed presently and by others (23) were apt to be masked by combining adipocytes from several depots. Second, adipocytes were harvested from fat pads taken at critically different time points after SD exposure in these two studies. Specifically, in the present study, we reasoned that the time to test for differences in lipolytic rates was during the dynamic period of lipid mobilization (i.e., the first 5 wk of SDs), rather than after the majority of the lipid mobilization had occurred (i.e., 10 wk or more after SD exposure; Ref. 5). By contrast, Atgie et al. (1) tested adipocytes harvested from hamsters after 11 wk of SDs; that is, near the lipid mass nadir (37). In addition, these two critical factors (WAT pad anatomical location and time since transfer to SDs) interact to differentially affect lipid mobilization such that during the first 5 wk of SDs, the more internally/viscerally located WAT pads show the highest degree of lipid mobilization compared with the more meager decreases shown by the subcutaneous WAT pads (5). Thus pooling adipocytes from WAT depots differentially sensitive to NE-stimulated lipolysis at a time of SD exposure when hamsters were near their body fat nadir may have compromised the ability of Atgie et al. (1) to detect photoperiod-induced enhancements in noradrenergically triggered lipid mobilization.
Two other studies have tested for alterations in lipolysis associated with the reversal of seasonal obesity. The alpine marmot (Marmota marmota) is a species that exhibits an internally rather than photoperiod-driven seasonal body fat rhythm (circannual rhythm) and reverses its obese state during hibernation by voluntarily fasting (13). These animals have decreased responsiveness to catecholamine-induced lipolysis in both gonadal WAT and subcutaneous WAT during this lipid-loss phase (14), an effect opposite to that seen in the present study when Siberian hamsters are mobilizing their fat stores. Djungarian hamsters (P. sungorus cambelli), a species closely related to Siberian hamsters, also reverse their LD-associated seasonal obesity when exposed to SDs (33), but they do so in a delayed manner compared with Siberian hamsters, exhibiting significant decreases in body and lipid mass beginning at ∼8 wk or more of SD exposure (33). SD Djungarian hamster adipocytes do not show enhanced sensitivity to NE-stimulated lipolysis or HSL activity (33), the latter being one of several enzymes involved in triacylglycerol catabolism. The adipocytes isolated in that study (33), however, derived from the “anterior subcutaneous WAT depot,” which we presume to be the dorsosubcutaneous WAT, and were tested at 2-wk intervals for 10 wk of SDs. This lack of an exaggerated SD-associated increase in NE-stimulated lipolysis may have been a result of testing their adipocytes before their lipolytic rate was maximal (i.e., only 2 wk after the first significant decrease in body fat by SDs). Thus these lipolysis tests in Djungarian hamsters may have been prematurely conducted relative to the phase of most rapid lipid mobilization. Moreover, if dorsosubcutaneous WAT shows SD-induced lipid mobilization similar to that of Siberian hamster subcutaneous WAT (IWAT; Ref. 5), then this depot may show delayed increases in lipolytic rate compared with visceral WAT (i.e., they may have tested a relatively unresponsive WAT depot). Alternatively for both studies, the lack of seasonally enhanced lipolysis may simply be due to species differences.
In our tests of the specific β3-adrenoceptor agonist BRL-37344, we did not address the possible role of the other β-adrenoceptor subtypes (β1-, β2-ARs) known to stimulate lipolysis (for review see Ref. 10). In addition, we did not specifically parcel out the possible role of two antilipolytic factors, α2-adrenoceptors (for review see Ref. 27) and adenosine, synthesized and released locally by white adipocytes (for review see Ref. 12) nor its associated A1-receptor. Adenosine has a marked antilipolytic effect on Siberian hamster white adipocytes, but this effect is not modulated by the photoperiod (1). In addition, we eliminated potential adenosine effects on lipolysis in the present study by adding ADA to destroy adenosine and replaced it with a synthetic nonmetabolizable adenosine analog (PIA). Moreover, because we tested the effects of NE on glycerol release, we thereby assessed the net effect of the opposing α2-adrenoceptor and β1–3-adrenoceptor effects on lipolysis (i.e., the interaction of α2-AR-mediated inhibition and β-AR-mediated activation) as well as any effects of adenosine via the A1-receptors. Thus any photoperiod-induced changes in the components of the signal transduction cascade from these receptors to and including second messenger changes, as well as hydrolysis of the triacylglycerols and the ultimate release of glycerol and free fatty acids from the adipocyte, would be included in our assays.
Collectively, the present results add to the composition of a picture showing physiological integration working toward the same end: reversal of the seasonal obesity that occurs in LDs by SD exposure in Siberian hamsters. First, the SD photoperiod is transduced into a biological signal via the duration of the nocturnal secretion of melatonin (6). The SD-induced increase in the duration of melatonin secretion, in turn, stimulates the MEL1a receptors located on the sympathetic outflow circuitry from brain to WAT (36) for a longer duration than in LDs, thereby increasing the duration of the sympathetic drive to WAT (40). Second, the SD-induced increase in sympathetic drive to WAT increases β3-adrenoceptor mRNA (17) and, likely, β3-adrenoceptors. Finally, on the basis of the present results, SDs increase both the efficacy and potency of the lipolytic responses to NE perhaps via the β3-adrenoceptor subtype. These SD responses, combined with the SD-induced increase in BAT thermogenesis occurring via another coordinated suite of physiological responses, promote oxidation of these mobilized lipids and simultaneously improve the ability of Siberian hamsters to tolerate the decreases in ambient temperature associated with fall/winter (38). Specifically, the sympathetic drive (NE turnover) to BAT increases in SDs (32). This results in increases in peroxisome proliferator-activated receptor-γ (PPARγ)/PPARγ coactivator-1 (PGC-1) signaling yielding increases in BAT UCP-1 mRNA [and likely increases in UCP-1 protein (17)], thereby promoting increases in BAT thermogenic capacity. This produces SD-induced increases in BAT thermogenic capacity (increased GDP-binding; Ref. 32) and improvement of nonshivering thermogenesis at the same time (39). In addition, SDs stimulate the ectopic expression of UCP-1 mRNA (and likely UCP-1 protein) in WAT (17), thus permitting the possible oxidation of lipid fuels in situ. Together, these sets of responses promote the shift from the obese to a leaner state by Siberian hamsters. This concerted physiological effort to decrease body fat by Siberian hamsters is in stark contrast to physiological forces opposing body fat loss in humans. Perhaps some aspects of the lessons learned about the mechanisms underlying the seasonally adaptive coordinated effort to decrease body fat by Siberian hamsters can be applied to help oppose the coordinated effort to retain body fat in humans.
This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01 DK-35254 (to T. J. Bartness), R01 DK-53903 (to R. B. S. Harris), and R01 DK-53872 and DK-64156 as well as American Diabetes Association Grant 1-03-RA-26 (to T. W. Gettys).
We thank Drs. Max Lafontan and Susan K. Fried and Heather Bowen for providing assistance with the lipolysis and glycerol release assay protocols. We thank Ruth F. Irvin, Nicole Rankine, Raven Jackson, and Walli Rahman for expert technical assistance and Thaddeus King and Quijiang W. Po for animal care.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2005 the American Physiological Society