Biomedical subjects

Timothy J Bartness

Publications and source records attributed to Timothy J Bartness.

At least 19 recordsLinked to original sources

PubMed2007

NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake.

Fasting triggers a constellation of physiological and behavioral changes, including increases in peripherally produced ghrelin and centrally produced hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most species; however, hamsters primarily increase foraging and food hoarding with smaller increases in food intake. Fasting-induced increases in foraging and food hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY, and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and subsequently NPY synthesis/release, it may be that fasting-induced increased hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging, food hoarding, and food intake? This was accomplished by injecting the NPY Y1 receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or given peripheral ghrelin injections and housed in a running wheel-based food delivery foraging system coupled with simulated-burrow housing. Three foraging conditions were used: 1) no running wheel access, free food, 2) running wheel access, free food, or 3) foraging requirement (10 revolutions/pellet) for food. Fasting was a more potent stimulator of foraging and food hoarding than ghrelin. Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced increased foraging and food intake and attenuated, but did not always completely block, fasting- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the NPY Y1 receptor is important for the effects of ghrelin- and fasting-induced increases in foraging and food intake, but other NPY receptors and/or other neurochemical systems are involved in increases in food hoarding.

Animals↗

PubMed2006

Social defeat and footshock increase body mass and adiposity in male Syrian hamsters.

Obesity is a world-wide epidemic, and many factors, including stress, have been linked to this growing trend. After social stress (i.e., defeat), subordinate laboratory rats and most laboratory mice become hypophagic and, subsequently, lose body mass; the opposite is true of subordinate Syrian hamsters. After social defeat, Syrian hamsters become hyperphagic and gain body mass compared with nonstressed controls. It is unknown whether this increase in body mass and food intake is limited to subordinate hamsters. In experiment 1, we asked, do dominant hamsters increase food intake, body mass, and adiposity after an agonistic encounter? Subordinate hamsters increased food intake and body mass compared with nonstressed controls. Although there was no difference in food intake or absolute body mass between dominant and nonstressed control animals, cumulative body mass gain was significantly higher in dominant than in nonstressed control animals. Total carcass lipid and white adipose tissue (WAT) (i.e., retroperitoneal and epididymal WAT) masses were significantly increased in subordinate, but not dominant, hamsters compared with nonstressed controls. In experiment 2, we asked, does footshock stress increase food intake, body mass, and adiposity. Hamsters exposed to defeat, but not footshock stress, increased food intake relative to nonstressed controls. In animals exposed to defeat or footshock stress, body mass, as well as mesenteric WAT mass, increased compared with nonstressed controls. Collectively, these data demonstrate that social and nonsocial stressors increase body and lipid mass in male hamsters, suggesting that this species may prove useful for studying the physiology of stress-induced obesity in some humans.

Adiposity↗

PubMed2006

Sympathetic but not sensory denervation stimulates white adipocyte proliferation.

White adipocyte proliferation is a hallmark of obesity, but it largely remains a mechanistic mystery. We and others previously demonstrated that surgical denervation of white adipose tissue (WAT) triggers increases in fat cell number, but it is unknown whether this was due to preadipocyte proliferation or maturation of existing preadipocytes that allowed them to be counted. In addition, surgical denervation severs not only sympathetic but also sensory innervation of WAT. Therefore, we tested whether sympathetic WAT denervation triggers adipocyte proliferation using 5-bromo-2'-deoxyuridine (BrdU) as a marker of proliferation and quantified BrdU-immunoreactive (ir) cells that were co-labeled with AD-3-ir, an adipocyte-specific membrane protein marker. The unilateral denervation model was used for all experiments where Siberian hamster inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham denervated serving as a within-animal control, and then BrdU was injected systemically for 6 days. When IWAT was surgically denervated, severing both sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker, were significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 300%. When IWAT was selectively sensory denervated via local microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH-ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was selectively sympathetically denervated via local microinjections of 6-hydroxy-dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 400%. Collectively, these data provide the first direct evidence that sympathetic nerves inhibit white adipocyte proliferation in vivo.

Adaptation, Physiological↗

PubMed2006

White adipose tissue lacks significant vagal innervation and immunohistochemical evidence of parasympathetic innervation.

Converging evidence indicates that white adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS) based on immunohistochemical labeling of a SNS marker (tyrosine hydroxylase [TH]), tract tracing of WAT sympathetic postganglionic innervation, pseudorabies virus (PRV) transneuronal labeling of WAT SNS outflow neurons, and functional evidence from denervation studies. Recently, WAT para-SNS (PSNS) innervation was suggested because local surgical WAT sympathectomy (sparing hypothesized parasympathetic innervation) followed by PRV injection yielded infected cells in the vagal dorsomotor nucleus (DMV), a traditionally-recognized PSNS brain stem site. In addition, local surgical PSNS WAT denervation triggered WAT catabolic responses. We tested histologically whether WAT was parasympathetically innervated by searching for PSNS markers in rat, and normal (C57BL) and obese (ob/ob) mouse WAT. Vesicular acetylcholine transporter, vasoactive intestinal peptide and neuronal nitric oxide synthase immunoreactivities were absent in WAT pads (retroperitoneal, epididymal, inguinal subcutaneous) from all animals. Nearly all nerves innervating WAT vasculature and parenchyma that were labeled with protein gene product 9.5 (PGP9.5; pan-nerve marker) also contained TH, attesting to pervasive SNS innervation. When Siberian hamster inguinal WAT was sympathetically denervated via local injections of catecholaminergic toxin 6-hydroxydopamine (sparing putative parasympathetic nerves), subsequent PRV injection resulted in no central nervous system (CNS) or sympathetic chain infections suggesting no PSNS innervation. By contrast, vehicle-injected WAT subsequently inoculated with PRV had typical CNS/sympathetic chain viral infection patterns. Collectively, these data indicate no parasympathetic nerve markers in WAT of several species, with sparse DMV innervation and question the claim of PSNS WAT innervation as well as its functional significance.

Adipose Tissue, White↗

PubMed2005

Social defeat increases food intake, body mass, and adiposity in Syrian hamsters.

Overeating and increases in body and fat mass are the most common responses to day-to-day stress in humans, whereas stressed laboratory rats and mice respond oppositely. Group housing of Syrian hamsters increases body mass, adiposity, and food intake, perhaps due to social confrontation-induced stress. In experiment 1 we asked, Does repeated social defeat increase food intake, body mass, and white adipose tissue (WAT) mass in Syrian hamsters? Male hamsters subjected to the resident-intruder social interaction model and defeated intermittently 15 times over 34 days for 7-min sessions significantly increased their food intake, body mass, and most WAT masses compared with nondefeated controls. Defeat significantly increased terminal adrenal norepinephrine, but not epinephrine, content. In experiment 2 we asked, Are 15 intermittent resident-intruder interactions necessary to increase body mass and food intake? Body mass and food intake of subordinate hamsters defeated only once were similar to those of nondefeated controls, but four or eight defeats similarly and significantly increased these responses. In experiment 3 we asked, Do intermittent defeats increase adiposity and food intake more than consecutive defeats? Four intermittent or consecutive defeats similarly and significantly increased food intake and body mass compared with nondefeated controls, but only intermittent defeats significantly increased all WAT masses. Consecutive defeats significantly increased mesenteric and inguinal WAT masses. Plasma leptin, but not insulin, concentrations were similarly and significantly increased compared with nondefeated controls. Collectively, social defeat, a natural stressor, significantly increased food intake, body mass, and adiposity in Syrian hamsters and may prove useful in determining mechanisms underlying human stress-induced obesity.

Adipose Tissue↗

PubMed2005

Energy expenditure and body composition of chronically maintained decerebrate rats in the fed and fasted condition.

The contribution of the caudal brainstem to adaptation to starvation was tested using chronically maintained decerebrate (CD) and neurologically intact controls. All rats were gavage fed an amount of diet that maintained weight gain in controls. CD rats were subjected to a two-stage surgery to produce a complete transection of the neuroaxis at the mesodiencephalic juncture. One week later, the rats were housed in an indirect calorimeter, and 24 h energy expenditure was measured for 4 d. One half of each of the CD and control groups was then starved for 48 h. Fed CD rats maintained a lower body temperature (35 C), a similar energy expenditure per unit fat-free mass but an elevated respiratory quotient compared with controls. They gained less weight, had 20% less lean tissue, and had 60% more fat than controls. Circulating leptin, adiponectin, and insulin were elevated, glucose was normal, but testosterone was dramatically reduced. Responses to starvation were similar in CD and controls; they reduced energy expenditure, decreased respiratory quotient, indicating lipid utilization, defended body temperature, mobilized fat, decreased serum leptin and insulin, and regulated plasma glucose. These data clearly demonstrate that the isolated caudal brainstem is sufficient to mediate many aspects of the energetic response to starvation. In intact animals, these responses may be refined by a contribution by more rostral brain areas or by communication between fore- and hind-brain. In the absence of communication from the forebrain, the caudal brainstem is inadequate for maintenance of testosterone levels or lean tissue in fed or fasted animals.

Adiponectin↗

PubMed2005

White adipose tissue sensory nerve denervation mimics lipectomy-induced compensatory increases in adiposity.

The sensory innervation of white adipose tissue (WAT) is indicated by the labeling of sensory bipolar neurons in the dorsal root ganglion after retrograde dye placement into WAT. In addition, immunoreactivity (ir) for sensory-associated neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P in WAT pads also supports the notion of WAT sensory innervation. The function of this sensory innervation is unknown but could involve conveying the degree of adiposity to the brain. In tests of total body fat regulation, partial surgical lipectomy triggers compensatory increases in the mass of nonexcised WAT, ultimately resulting in restoration of total body fat levels in Siberian hamsters and other animals. The signal that triggers this compensation is unknown but could involve disruption of WAT sensory innervation that accompanies lipectomy. Therefore, a local and selective sensory denervation was accomplished by microinjecting the sensory nerve neurotoxin capsaicin bilaterally into epididymal WAT (EWAT) of Siberian hamsters, whereas controls received vehicle injections. Additional hamsters had bilateral EWAT lipectomy (EWATx) or sham lipectomy. As seen previously, EWATx resulted in significantly increased retroperitoneal WAT (RWAT) and inguinal WAT (IWAT) masses. Capsaicin treatment significantly decreased CGRP- but not tyrosine hydroxylase-ir, attesting to the diminished and selective sensory innervation. Capsaicin-treated hamsters also had increased RWAT and, to a lesser degree, IWAT mass largely mimicking the WAT mass increases seen after lipectomy. Collectively, these data suggest the possibility that information related to peripheral lipid stores may be conveyed to the brain via the sensory innervation of WAT.

Adaptation, Physiological↗

PubMed2005

Effects of white adipose tissue grafts on total body fat and cellularity are dependent on graft type and location.

Surgical removal of body fat (lipectomy) triggers compensatory increases in nonexcised white adipose tissue (WAT), thus restoring adiposity levels in many species, including Siberian hamsters. In Siberian hamsters, when their lipectomized WAT is transplanted to another site (autologous grafts, no net change in body fat), healthy grafts result, but the lipectomy-induced compensatory increases in nonexcised WAT masses are exaggerated, an effect that apparently occurs only when the grafts contact intact WAT. When WAT is added to nonlipectomized hamsters to increase body fat, native WAT pads do not decrease. Thus WAT addition or removal-replacement does not induce compensatory WAT responses consistent with total body fat regulation as does WAT subtraction. Therefore, we tested whether the exaggerated response to lipectomy occurring with autologous WAT transplantation is dependent on graft site placement and whether the donor graft source [inguinal or epididymal WAT (IWAT, EWAT), sibling vs. nonsibling] affected body fat responses to WAT additions in nonlipectomized hamsters. Lipectomized hamsters received subcutaneous autologous EWAT grafts placed remotely from other WAT (ventrum) or in contact with intact WAT (dorsum), whereas intact hamsters received EWAT or IWAT grafts from sibling or nonsibling donors. The exaggerated response to lipectomy only occurred when grafts were in contact with intact WAT. EWAT, but not IWAT, additions to nonlipectomized siblings or nonsiblings increased native IWAT and retroperitoneal WAT mass but not EWAT mass compared with controls. Collectively, WAT transplantation to either lipectomized or nonlipectomized hamsters increased body fat contingent on graft contact with intact or native WAT.

Adaptation, Physiological↗

PubMed2005

Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin.

Leptin increases sympathetic nervous system (SNS) activity in brown adipose tissue and renal nerves. Experiments described here tested whether SNS innervation is required for peripheral, physiological concentrations of leptin to reduce body fat. In experiment 1, one epididymal (EPI) fat pad was sympathectomized by local injection of 6-hydroxydopamine (6OHDA) in C57BL/6 mice that were then infused for 13 days with PBS or 10 microg leptin/day from an intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total body fat of PBS-infused mice but leptin decreased the size of both injected and noninjected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use of male Sprague-Dawley rats that were infused with 50 microg leptin/day. Leptin had little effect on EPI weight or norepinephrine (NE) content, but denervation of one EPI pad decreased the effect of leptin on intact EPI, inguinal and retroperitoneal (RP) fat and increased the size of the mesenteric fat pad. Experiment 3 included groups in which either one EPI or one RP pad was denervated. RP denervation reduced RP NE content but did not prevent a leptin-induced reduction in fat pad mass. Therefore, the SNS is not required for low doses of leptin to reduce body fat. EPI denervation significantly increased adipocyte number in contralateral EPI and RP fat pads and this was prevented by leptin. These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots.

Adipose Tissue↗

PubMed2005

Role of NPY and its receptor subtypes in foraging, food hoarding, and food intake by Siberian hamsters.

Fasting has widespread physiological and behavioral effects such as increases in arcuate nucleus neuropeptide Y (NPY) gene expression in rodents, including Siberian hamsters. Fasting also stimulates foraging and food hoarding (appetitive ingestive behaviors) by Siberian hamsters but does relatively little to change food intake (consummatory ingestive behavior). Therefore, we tested the effects of third ventricular NPY Y1 ([Pro(34)]NPY) or Y5 ([D-Trp(34)]NPY) receptor agonists on these ingestive behaviors using a wheel running-based food delivery system coupled with simulated burrow housing. Siberian hamsters had 1) no running wheel access and free food, 2) running wheel access and free food, or 3) foraging requirements (10 or 50 revolutions/pellet). NPY (1.76 nmol) stimulated food intake only during the first 4 h postinjection ( approximately 200-1,000%) and mostly in hamsters with a foraging requirement. The Y1 receptor agonist markedly increased food hoarding (250-1,000%), increased foraging as well as wheel running per se, and had relatively little effect on food intake (<250%). Unlike NPY, the Y5 agonist significantly increased food intake, especially in foraging animals ( approximately 225-800%), marginally increased food hoarding (250-500%), and stimulated foraging and wheel running 4-24 h postinjection, with the distribution of earned pellets favoring eating versus hoarding across time. Across treatments, food hoarding predominated early postinjection, whereas food intake tended to do so later. Collectively, NPY stimulated both appetitive and consummatory ingestive behaviors in Siberian hamsters involving Y1/Y5 receptors, with food hoarding and foraging/wheel running (appetitive) more involved with Y1 receptors and food intake (consummatory) with Y5 receptors.

Animals↗

PubMed2005

New developments in tracing neural circuits with herpesviruses.

Certain neurotropic viruses can invade the nervous system of their hosts and spread in chains of synaptically connected neurons. Consequently, it is possible to identify entire hierarchically connected circuits within an animal. In this review, we discuss the use of neurotropic herpesviruses as neuronal tract tracers. Although a variety of tract tracing viruses are available, each with its own unique infection characteristics, we focus on the widespread use of attenuated strains of pseudorabies virus (PRV), a swine herpesvirus with a broad host range. In particular, we focus on new applications of PRV for tract tracing including use of multiple infections by PRV reporter viruses to test for circuit convergence/divergence within the same animal. We provide examples of these combined application techniques within the context of an animal model to study the naturally occurring reversal of seasonal obesity in Siberian hamsters.

Animals↗

PubMed2005

Brain-adipose tissue cross talk.

While investigating the reversible seasonal obesity of Siberian hamsters, direct sympathetic nervous system (SNS) postganglionic innervation of white adipose tissue (WAT) has been demonstrated using anterograde and retrograde tract tracers. The primary function of this innervation is lipid mobilization. The brain SNS outflow to WAT has been defined using the pseudorabies virus (PRV), a retrograde transneuronal tract tracer. These PRV-labelled SNS outflow neurons are extensively co-localized with melanocortin-4 receptor mRNA, which, combined with functional data, suggests their involvement in lipolysis. The SNS innervation of WAT also regulates fat cell number, as noradrenaline inhibits and WAT denervation stimulates fat cell proliferation in vitro and in vivo respectively. The sensory innervation of WAT has been demonstrated by retrograde tract tracing, electrophysiological recording and labelling of the sensory-associated neuropeptide calcitonin gene-related peptide in WAT. Local injections of the sensory nerve neurotoxin capsaicin into WAT selectively destroy this innervation. Just as surgical removal of WAT pads triggers compensatory increases in lipid accretion by non-excised WAT depots, capsaicin-induced sensory denervation triggers increases in lipid accretion of non-capsaicin-injected WAT depots, suggesting that these nerves convey information about body fat levels to the brain. Finally, parasympathetic nervous system innervation of WAT has been suggested, but the recent finding of no WAT immunoreactivity for the possible parasympathetic marker vesicular acetylcholine transporter (VAChT) argues against this claim. Collectively, these data suggest several roles for efferent and afferent neural innervation of WAT in body fat regulation.

Adipose Tissue↗

PubMed2005

Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue.

Energy balance results from the coordination of multiple pathways affecting energy expenditure and food intake. Candidate neuropeptides involved in energy balance are the melanocortins. Several species, including Siberian hamsters studied here, decrease and increase food intake in response to stimulation and blockade of the melanocortin 4-receptor (MC4-R). In addition, central application of the MC3/4-R agonist melanotan-II decreases body fat (increases lipolysis) beyond that accounted for by its ability to decrease food intake. Because an increase in the sympathetic nervous system drive to white adipose tissue (WAT) is the principal initiator of lipolysis, we tested whether the sympathetic outflow circuitry from brain to WAT contained MC4-R mRNA expressing cells. This was accomplished by labeling the sympathetic outflow to inguinal WAT using the pseudorabies virus (PRV), a transneuronal retrograde viral tract tracer, and then processing the brain for colocalization of PRV immunoreactivity with MC4-R mRNA, the latter assessed by in situ hybridization. MC4-R mRNA was impressively colocalized in PRV-labeled cells (approximately greater than 60%) in many brain areas across the neuroaxis, including those typically implicated in lipid mobilization (e.g., hypothalamic paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, lateral hypothalamic area), as well as those not traditionally identified with lipolysis (e.g., preoptic area, subzona incerta of the lateral hypothalamus, periaqueductal gray, solitary nucleus). These data provide compelling neuroanatomical evidence that could underlie a direct central modulation of the sympathetic outflow to WAT by the melanocortins through the MC4-Rs resulting in changes in lipid mobilization and adiposity.

Adipose Tissue↗

PubMed2005

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

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 beta3-adrenoceptor (beta3-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 beta3-AR mRNA expression, suggest that increased beta3-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.

Adipocytes↗

PubMed2004

Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters.

Fasting triggers many effects, including increases in circulating concentrations of ghrelin, a primarily stomach-derived orexigenic hormone. Exogenous ghrelin treatment stimulates food intake, implicating it in fasting-induced increases in feeding, a consummatory ingestive behavior. In Siberian hamsters, fasting also stimulates appetitive ingestive behaviors such as foraging and food hoarding. Therefore, we tested whether systemic ghrelin injections (3, 30, and 200 mg/kg) would stimulate these appetitive behaviors using a running wheel-based food delivery system coupled with simulated burrow housing. We also measured active ghrelin plasma concentrations after exogenous ghrelin treatment and compared them to those associated with fasting. Hamsters had the following: 1) no running wheel access, free food; 2) running wheel access, free food; or 3) foraging requirement (10 revolutions/pellet), no free food. Ghrelin stimulated foraging at 0-1, 2-4, and 4-24 h postinjection but failed to affect wheel running activity not coupled to food. Ghrelin stimulated food intake initially (200-350%, first 4 h) across all groups; however, in hamsters with a foraging requirement, ghrelin also stimulated food intake 4-24 h postinjection (200-250%). Ghrelin stimulated food hoarding 2-72 h postinjection (100-300%), most markedly 2-4 h postinjection in animals lacking a foraging requirement (635%). Fasting increased plasma active ghrelin concentrations in a time-dependent fashion, with the 3- and 30-mg/kg dose creating concentrations of the peptide comparable to those induced by 24-48 h of fasting. Collectively, these data suggest that exogenous ghrelin, similar to fasting, increases appetitive behaviors (foraging, hoarding) by Siberian hamsters, but dissimilar to fasting in this species, stimulates food intake.

Animals↗

PubMed2004

Sensory or sympathetic white adipose tissue denervation differentially affects depot growth and cellularity.

Functional and histological evidence for the sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) exists for several species; however, its sensory innervation has only been shown in laboratory rats, and its function is unclear. We tested the effects of sensory and SNS innervation of Siberian hamster epididymal and inguinal WAT (EWAT and IWAT) by assessing calcitonin gene-related peptide (CGRP)- and tyrosine hydroxylase-immunoreactivity (ir), respectively. Next, we tested the role of the sensory innervation of WAT on growth and cellularity because WAT surgical denervation increases pad mass via selective increases in fat cell number, an effect ascribed to SNS denervation but that could be due to the accompanying surgical disruption of WAT sensory innervation. Sensory denervation was accomplished via multiple local microinjections of capsaicin into WAT, and its effects were compared with those of surgical denervation. Surgically denervated IWAT and EWAT showed significantly decreased tyrosine hydroxylase-ir and CGRP-ir, whereas capsaicin-treated WAT had only significantly decreased CGRP-ir. Surgically denervated pad masses were significantly increased; this was accompanied by increased total fat cell number in IWAT, with no change in fat cell size. EWAT only showed a significant increase in the number of small- to medium-sized adipocytes (75-125 mum diameter). By contrast, sensory-denervated pad masses were unchanged, but IWAT showed significantly increased average fat cell size. Collectively, these data provide immunohistochemical evidence for sensory and SNS innervation of WAT in Siberian hamsters and differential control of WAT cellularity by these innervations, as well as the ability of locally applied capsaicin to selectively reduce WAT sensory innervation.

Adipocytes↗

PubMed2004

Compensation for an increase in body fat caused by donor transplants into mice.

Rodents tend to compensate for experimental obesity in which both adipocyte size and number are increased. In contrast, it was recently reported that Siberian hamsters do not compensate for dorsal subcutaneous transplants of fat, which increase body fat without changing the size of adipocytes. In the first experiment described here we tested whether mice changed the size of their endogenous fat stores 2 or 5 wk after donor fat was added as subcutaneous transplants. Each epididymal fat pad from donor mice was cut in half and placed ventrally in recipient mice, increasing body fat by approximately 10%. After 2 wk, there was no effect of the transplants on the size of endogenous fat depots or the size of adipocytes in epididymal fat depots. There was a substantial decrease in mass and adipocyte size in transplanted fat. Five weeks after surgery the endogenous epididymal and retroperitoneal fat depots of recipient mice were significantly decreased, serum leptin was reduced, and the size of adipocytes in endogenous epididymal fat was significantly reduced, although cell number had not changed. The size of transplanted cells was the same as at 2 wk. In a second experiment, epididymal fat was placed as either dorsal or ventral subcutaneous fat transplants. Five weeks after surgery the endogenous fat depots were decreased in all recipient mice but none of the differences reached statistical significance. These results suggest that mice have mechanisms to maintain total body fat mass that respond to an increase in the number of fat cells present.

Adipocytes↗

PubMed2004

Norepinephrine turnover in brown and white adipose tissue after partial lipectomy.

Total body fat is restored after the surgical removal (i.e., partial lipectomy) of white adipose tissue (WAT), and this is accomplished via increases in the mass of nonexcised WAT pads. The underlying mechanism for this apparent regulation of total body fat is unknown. One possibility is via the sympathetic nervous system (SNS) innervation of WAT and brown adipose tissue (BAT) through the regulation of lipolysis and thermogenesis, respectively. Specifically, decreases in SNS activity might fuel lipectomy-induced body fat compensation through energy saved from decreased BAT thermogenesis and would promote lipid accretion through decreased WAT basal lipolysis. Therefore, we tested whether lipectomy triggered decreases in the SNS drive [as indicated by the norepinephrine turnover (NETO)] to nonexcised WAT or to BAT, at times before the lipectomy-induced fat pad mass compensation was complete. Siberian hamsters received either sham or bilateral epididymal WAT lipectomy, and NETO was measured in the remaining WAT and interscapular BAT (IBAT) before, and 3 and 6 weeks after surgery. Total dissected WAT, and inguinal and retroperitoneal WAT masses were significantly increased following lipectomy, whereas dorsal subcutaneous WAT and IBAT masses, as well as food intake, were unchanged. The only significant change in NETO was a marked decrease (approximately 90%) in IBAT NETO at Week 3 postlipectomy compared with the sham-lipectomized controls. These findings suggest that the lipid accretion of nonexcised WAT pads triggered by lipectomy may be partially fueled by decreased BAT thermogenesis, inasmuch as decreased IBAT NETO reflects decreased BAT heat production.

Adipose Tissue↗