The role of the vgf gene and VGF-derived peptides in nutrition and metabolism

Bartolomucci, Alessandro; Possenti, Roberta; Levi, Andrea; Pavone, Flaminia; Moles, Anna

doi:10.1007/s12263-007-0047-0

Cited by 46 publications

(54 citation statements)

References 102 publications

(153 reference statements)

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“…1002; final volume of 100 ll; flow rate 0.25 ll/h, corresponding to 15 lg/day of TLQP-21) connected to the Alzet brain infusion kit. The dose was selected based on previous studies [7][8][9][10]. To allow preloading, pumps were filled the day before surgery and overnight incubated in sterile saline at 37°C.…”

Section: Peptidementioning

confidence: 99%

“…Among the different VGF-peptides, however, only the peptide designate TLQP-21 was demonstrated to exert a catabolic role [7,37], while preliminary data showed an orexigenic effect following acute injection of the peptides designated TLQP-62 and HHPD-41 [8]. In particular, Bartolomucci et al [7] proved that chronic icv injection of TLQP-21 increased resting energy expenditure and prevented the early phase of diet-induced obesity and associated leptin and ghrelin alterations.…”

Section: Introductionmentioning

confidence: 99%

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Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

et al. 2009

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The vgf gene regulates energy homeostasis and the VGF-derived peptide TLQP-21 centrally exerts catabolic effects in mice and hamsters. Here, we investigate the effect of chronic intracerebroventricular (icv) injection of TLQP-21 in mice fed high fat diet (HFD). Fast weightgaining mice injected with the peptide or cerebrospinal fluid were selected for physiological, endocrine, and molecular analysis. TLQP-21 selectively inhibited the increase in body weight and epididymal white adipose tissue (eWAT) weight induced by HFD in control animals despite both groups having a similar degree of hyperphagia. TLQP-21 normalized the increase in leptin and decrease in ghrelin while increasing epinephrine and epinephrine/norepinephrine ratio when compared to values in controls. Finally, HFD-TLQP-21 mice showed a selective increase of eWAT b3-adrenergic receptor mRNA. Peroxisome-proliferatoractivated-receptor-d and hormone-sensing-lipase mRNA were also upregulated. In conclusion, chronic icv infusion of TLQP-21 prevented the early phase of diet-induced obesity despite overfeeding. These effects were paralleled by activation of catabolic pathways within the eWAT. Our results further support a role for TLQP-21 as a catabolic neuropeptide.

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Section: Peptidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

et al. 2009

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“…injection of the naturally occurring VGF-derived TLQP-21 peptide increased energy expenditure and body temperature, and prevented diet-induced obesity in mice (Bartolomucci et al 2006), while reducing food intake in Siberian hamsters (Jethwa et al 2007). It was proposed that further end products of the VGF precursor (yet to be characterised) could be responsible for inhibiting energy expenditure, thus explaining the relevant aspects of the knockout phenotype (Bartolomucci et al 2007, Jethwa & Ebling 2008.…”

Section: Introductionmentioning

confidence: 99%

“…In cells and tissues, proteolytic processing yields diverse peptides, including some of low MW, which were preferentially released by various stimuli (Possenti et al 1989, Trani et al 1995. These include peptides encompassing the VGF C-terminal portion, TLQP-21 and TLQP-62 peptides, and the recently identified peptides NERP-1 and -2 (Trani et al 2002, Bartolomucci et al 2007, Yamaguchi et al 2007, Bozdagi et al 2008. While vgf gene expression is distinctly modulated in multiple models and conditions (Levi et al 2004), differential processing and modulation of VGF peptides have been shown so far in the pituitary (Brancia et al 2005), adrenal glands (D'Amato et al 2008) and pancreas (Cocco et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding

Brancia¹,

Cocco²,

D'Amato³

et al. 2010

Journal of Endocrinology

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Although vgf gene knockout mice are hypermetabolic, administration of the VGF peptide TLQP-21 itself increased energy consumption. Agonist-antagonist roles are thus suggested for different VGF peptides, and the definition of their tissue heterogeneity is mandatory. We studied the rat stomach using antisera to C-or N-terminal sequences of known or predicted VGF peptides in immunohistochemistry and ELISA. TLQP (rat VGF 556-565 ) peptide/s were most abundant (162G11 pmol/g, meanGS.E.M.) and were brightly immunostained in enterochromaffin-like (ECL) cells and somatostatin cells. A peptide co-eluting with TLQP-21 was revealed in HPLC of gastric and hypothalamic extracts, while the extended TLQP-62 form was restricted to the hypothalamus. Novel PGH (rat VGF 422-430 ) peptide/s were revealed in ghrelin cells, mostly corresponding to low MW forms (0 . 8-1 . 5 kDa), while VGF C-terminus peptides were confined to neurons. VGF mRNA was present in the above gastric endocrine cell types, and was prominent in chief cells, in parallel with low-intensity staining for further cleaved products from the C-terminal region of VGF (HVLL peptides: VGF 605-614 ). In swine stomach, a comparable profile of VGF peptides was revealed by immunohistochemistry. When fed and fasted rats were studied, a clear-cut, selective decrease on fasting was observed for TLQP peptides only (162G11 vs 74G5 . 3 pmol/g, fed versus fasted rats, meanGS.E.M., P!0 . 00001). In conclusion, specific VGF peptides appear to be widely represented in different gastric endocrine and other mucosal cell populations. The selective modulation of TLQP peptides suggests their involvement in peripheral neuro-endocrine mechanisms related to feeding responses and/or ECL cell regulation.

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“…Interestingly, these findings are the opposite of what the VGF germline knockout would have predicted. It has been hypothesized that these contrasting findings are due to bioactive peptides derived from VGF peptide precursor having antagonistic functions, e.g., TLQP-21 is catabolic, whereas neuroendocrine regulatory peptide-2 is anabolic (31,32). Notably, VGF peptides have also shown heterogeneous expression in several neuroendocrine tissues including the stomach and pancreas (30,33).…”

mentioning

confidence: 99%

Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice

2015

EndocrinologyJN

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Environmental enrichment (EE), a housing condition providing complex physical, social, and cognitive stimulation, leads to improved metabolic health and resistance to diet-induced obesity and cancer. One underlying mechanism is the activation of the hypothalamic-sympathoneuraladipocyte axis with hypothalamic brain-derived neurotrophic factor (BDNF) as the key mediator. VGF, a peptide precursor particularly abundant in the hypothalamus, was up-regulated by EE. Overexpressing BDNF or acute injection of BDNF protein to the hypothalamus up-regulated VGF, whereas suppressing BDNF signaling down-regulated VGF expression. Moreover, hypothalamic VGF expression was regulated by leptin, melanocortin receptor agonist, and food deprivation mostly paralleled to BDNF expression. Recombinant adeno-associated virus-mediated gene transfer of Cre recombinase to floxed VGF mice specifically decreased VGF expression in the hypothalamus. In contrast to the lean and hypermetabolic phenotype of homozygous germline VGF knockout mice, specific knockdown of hypothalamic VGF in male adult mice led to increased adiposity, decreased core body temperature, reduced energy expenditure, and impaired glucose tolerance, as well as disturbance of molecular features of brown and white adipose tissues without effects on food intake. However, VGF knockdown failed to block the EE-induced BDNF upregulation or decrease of adiposity indicating a minor role of VGF in the hypothalamicsympathoneural-adipocyte axis. Taken together, our results suggest hypothalamic VGF responds to environmental demands and plays an important role in energy balance and glycemic control likely acting in the melanocortin pathway downstream of BDNF. (Endocrinology 2016(Endocrinology : 34-46, 2016 I n 2014, 52% of adults worldwide were overweight or obese, thus this epidemic has undoubtedly become a global health, social, and economic problem (1, 2). Substantial obesity-related morbidity and mortality have prompted many investigations to explore genes involved in metabolic regulation. We previously manipulated the environment and demonstrated that environ-mental enrichment (EE), a housing condition providing complex stimuli, leads to robust improvements in metabolism including decreased adiposity, resistance to diet-induced obesity, and mitigation of obesity-associated liver steatosis and insulin resistance in addition to inhibition of peripheral cancers (3-5). Moreover, our mechanistic studies have elucidated a novel neuroendocrine axis, the hypothalamic-sympathoneural-adipocyte (HSA) axis, underlying the EE-induced resistance to obesity and

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The role of the vgf gene and VGF-derived peptides in nutrition and metabolism

Cited by 46 publications

References 102 publications

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding

Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice

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