Photoperiod regulates arcuate nucleus POMC, AGRP, and  leptin receptor mRNA in Siberian hamster hypothalamus

Mercer, Julian G.; Moar, Kim-Marie; Ross, Alexander; Hoggard, Nigel; Morgan, Peter J.

doi:10.1152/ajpregu.2000.278.1.r271

Cited by 117 publications

(170 citation statements)

References 51 publications

(65 reference statements)

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“…Possible reasons are: (i) gene expression for AGRP was unresponsive to the increasing circulating concentrations of insulin and leptin, (ii) AGRP had a greater response time than NPY to the circulatory changes in insulin and leptin, (iii) there was a greater initial level of expression in animals of the HI group, attributable to their low initial BC, and expression was still decreasing after 4 weeks, or (iv) AGRP gene expression is regulated by other factor(s). Since AGRP and NPY mRNAs are co-expressed within the ARC of rodents (Mercer et al 2000), findings from the present study suggest either that there was transcriptspecific regulation within NPY/AGRP-expressing neurons or that different neuronal sub-populations were activated.…”

Section: Discussionmentioning

confidence: 64%

“…The CART probe was generated from a cloned sheep cDNA as described previously (Barrett et al 2001). AGRP and POMC probes were generated from cloned Siberian hamster cDNAs (Mercer et al 2000) and have been validated on sheep brain tissue . Briefly, sections were fixed, acetylated, and hybridised overnight at 58 C using 35 S-labelled cRNA probes (1-1·5 107 c.p.m./ml).…”

Section: Hypothalamic Gene Expressionmentioning

confidence: 99%

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Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

Archer¹,

Rhind²,

Findlay³

et al. 2002

Journal of Endocrinology

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Body reserves (long-term) and food intake (short-term) both contribute nutritional feedback to the hypothalamus. Reproductive neuroendocrine output (GnRH/LH) is stimulated by increased food intake and not by high adiposity in sheep, but it is unknown whether appetiteregulating hypothalamic neurons show this differential response. Castrated male sheep (Scottish Blackface) with oestradiol implants were studied in two 4 week experiments. In Experiment 1, sheep were fed to maintain the initial body condition (BC) score of 2·0 0·00 (lower BC (LBC), n=7) or 2·9 0·09 (higher BC (HBC), n=9), and liveweight of 43 1·1 and 59 1·6 kg respectively. LBC and HBC sheep had similar mean plasma LH concentration, pulse frequency and amplitude, but HBC animals had higher mean plasma concentrations of insulin (P<0·01), leptin (P<0·01) and glucose (P<0·01). Gene expression (measured by in situ hybridisation) in the hypothalamic arcuate nucleus (ARC) was higher in LBC than HBC sheep for neuropeptide Y (NPY; 486% of HBC, P<0·01), agouti-related peptide (AGRP; 467%, P<0·05) and leptin receptor (OB-Rb; 141%, P<0·05), but lower for cocaine-and amphetamine-regulated transcript (CART; 92%, P<0·05) and similar between groups for pro-opiomelanocortin (POMC). In Experiment 2, sheep with initial mean BC score 2·4 0·03 and liveweight 55 0·8 kg were fed a liveweight-maintenance ration (low intake, LI, n=7) while sheep with initial mean BC score 2·0 0·03 and liveweight 43 1·4 kg were fed freely so that BC score increased to 2·5 0·00 and liveweight increased to 54 1·4 kg (high intake, HI, n=9). Compared with LI, HI sheep had higher mean plasma LH (P<0·05), baseline LH (P<0·01) and pulse amplitude (P<0·01) and showed a trend towards higher pulse frequency. Although there were no differences in final mean plasma concentrations, there were significant increases over time in mean concentrations of insulin (P<0·001), leptin (P<0·05) and glucose (P<0·001) in HI sheep. Gene expression for AGRP in the ARC was higher in HI than LI animals (453% of LI; P<0·05), but expression levels were similar for NPY, OB-Rb, CART and POMC. Thus, the hypothalamus shows differential responses to steady-state adiposity as opposed to an increase in food intake, in terms of both reproductive neuroendocrine activity and hypothalamic appetiteregulating pathways. Differences in hypothalamic gene expression were largely consistent with contemporary levels of systemic leptin and insulin feedback; however, increased nutritional feedback was stimulatory to GnRH/LH whereas constant high feedback was not. The hypothalamus therefore has the ability to retain a nutritional memory that can influence subsequent responses.

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Section: Discussionmentioning

confidence: 64%

Section: Hypothalamic Gene Expressionmentioning

confidence: 99%

Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

Archer¹,

Rhind²,

Findlay³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…This indicated that testosterone, circulating concentrations of which would have been elevated in SD given the increased testis size (Lincoln & Davidson 1977), might be either directly down-regulating AGRP gene expression or indirectly facilitating down-regulation of AGRP by SD. Such an effect of testosterone has not been reported in the literature but it is noteworthy that AGRP gene expression is conversely decreased in male Siberian hamsters in LD when their circulating testosterone is highest (Mercer et al 2000b). Furthermore, AGRP gene expression was decreased in SD hamsters given subcutaneous implants to raise systemic testosterone concentrations (J G Mercer, personal communication) and AGRP gene expression is apparently not regulated by photoperiod in female Siberian hamsters .…”

Section: Nutritional Status and Hypothalamic Gene Expression · Z A Armentioning

confidence: 96%

“…The NPY probe was generated from a 500 bp fragment of rat prepro-NPY cDNA and has been validated for use on sheep tissues (Adam et al 1997). The CART probe (used only in experiment 2) was generated from a cloned sheep 299 bp cDNA as described previously (Barrett et al 2001), and AGRP and POMC probes were generated from cloned Siberian hamster cDNA fragments of 229 bp and 344 bp respectively (Mercer et al 2000b) and have been validated in sheep brain . Briefly, sections were fixed, acetylated and hybridised overnight at 58 C using 35S-labelled cRNA probes (1-1·5×10 7 c.p.m./ml).…”

Section: In Situ Hybridisationmentioning

confidence: 99%

Effects of nutritional status and gonadal steroids on expression of appetite-regulatory genes in the hypothalamic arcuate nucleus of sheep

Archer¹,

Findlay²,

McMillen³

et al. 2004

Journal of Endocrinology

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Sheep exhibit photoperiod-driven seasonal changes in appetite and body weight so that nutritional status increases in long days (LD) and decreases in short days (SD); additionally, they are reproductively active in SD and inactive in LD. We addressed the hypothesis that appetite-regulatory genes in the hypothalamus respond differently to changes in nutritional feedback induced by photoperiod as opposed to food restriction, and that responses would be influenced by gonadal steroid status. Castrated oestradiol-implanted male sheep were kept in SD (8 h light/day) or LD (16 h light/day) for 11 weeks, with ad libitum or restricted food (experiment 1; n=8/ group). Rams were kept in SD or LD for 12 weeks with ad libitum or restricted food (experiment 2; n=6/group). Gene expression (by in situ hybridisation) in the hypothalamic arcuate nucleus for leptin receptor (OB-Rb), neuropeptide Y (NPY), pro-opiomelanocortin (POMC) and agouti-related peptide (AGRP) was unaffected by photoperiod treatment, but food restriction increased NPY and AGRP mRNAs, in experiment 1. In experiment 2, mRNAs for POMC and cocaine-and amphetamineregulated transcript (CART) were up-regulated and AGRP down-regulated in SD, while food restriction increased OB-Rb mRNA, increased NPY and AGRP mRNAs only in LD and decreased POMC mRNA only in SD. Thus, gene expression responded differently to photoperiod and food restriction, and the melanocortin pathway was up-regulated in SD in reproductively activated rams but not in oestradiol-implanted castrates. These data support the hypothesis that hypothalamic appetiteregulatory pathways respond differently to changes in nutritional feedback induced by photoperiod as opposed to food restriction, with gonadal steroid feedback additionally influencing the responses.

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“…After 12-18 weeks, hamsters lose approximately 30-40% of their initial body mass, with more than half of this being attributed to mobilization of fat reserves (Ebling 1994, Bartness 1996, Klingenspor et al 2000, Mercer et al 2000. In contrast, Syrian hamsters and collared lemmings have their maximum body masses in the winter (Bartness & Wade 1985).…”

Section: Studies Of Other Speciesmentioning

confidence: 99%

The contribution of animal models to the study of obesity

et al. 2008

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SummaryObesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such geneticallyengineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy balance. Despite all this work, there are many gaps in our understanding of how body composition and energy storage are regulated, and a continuing need for the development of pharmaceuticals to treat obesity. Accordingly, reductions in the use of animal models, while ethically desirable, will not be feasible in the short to medium term, and indeed an expansion in activity using animal models is anticipated as the epidemic continues and spreads geographically.

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Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus

Cited by 117 publications

References 51 publications

Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

Effects of nutritional status and gonadal steroids on expression of appetite-regulatory genes in the hypothalamic arcuate nucleus of sheep

The contribution of animal models to the study of obesity

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