Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure

Watson, Elizabeth E.; Fargali, Samira; Okamoto, Haruka; Sadahiro, Masato; Gordon, Ronald E.; Chakraborty, Tandra R.; Sleeman, Mark W.; Salton, Stephen R.J.

doi:10.1186/1472-6793-9-19

Cited by 37 publications

(41 citation statements)

References 102 publications

(123 reference statements)

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“…On the whole, increased energy consumption appeared to be the major change in vgf À/À mice, with associated features such as greatly reduced fertility (ibidem). More recently, novel vgf knock-out mice, back-crossed in the C57BL6/J strain for more than ten generations, showed the phenotype of high energy consumption, but not the high locomotor activity (Watson et al, 2009). An increased sympathetic drive to fat tissue appeared to induce increased lipolysis, decreased lipogenesis, and brown adipocyte differentiation in white adipose tissue (ibidem).…”

Section: Knock-out Phenotypementioning

confidence: 97%

“…In sympathetic ganglia, VGF is well represented in neurons, axons and intraganglionic terminals (Ferri et al, 1992), in parallel with its mRNA (Watson et al, 2009). The possible presence of VGF peptides in the nerve supply to fat tissues (Watson et al, 2009) awaits clarification.…”

Section: Spinal Cord and Sensory Neurons Sympathetic Neuronsmentioning

confidence: 99%

“…The possible presence of VGF peptides in the nerve supply to fat tissues (Watson et al, 2009) awaits clarification.…”

Section: Spinal Cord and Sensory Neurons Sympathetic Neuronsmentioning

confidence: 99%

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VGF: An inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

Ferri

Noli

Brancia

et al. 2011

Journal of Chemical Neuroanatomy

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Section: Knock-out Phenotypementioning

confidence: 97%

Section: Spinal Cord and Sensory Neurons Sympathetic Neuronsmentioning

confidence: 99%

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VGF: An inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

Ferri

Noli

Brancia

et al. 2011

Journal of Chemical Neuroanatomy

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“…Deletion of the mouse vgf gene (knockout) resulted in thin, small, hyperactive and hypermetabolic animals (Hahm et al 1999), with derangement of hypothalamic outflow pathways regulating peripheral metabolic tissues and energy homoeostasis (Hahm et al 2002). More recently, an increased sympathetic drive in VgfK/K mice appeared to induce increased lipolysis, decreased lipogenesis and brown adipocyte differentiation in white adipose tissue (Watson et al 2009). Surprisingly, i.c.v.…”

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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“…Homozygous VGF germline knockout mice are small, lean, hypermetabolic, infertile, and have shortened life span (22). The metabolic phenotype is associated with decreased fat storage, increased fatty acid oxidation, increased uncoupling protein 1 (UCP1) expression in BAT, increased lipolysis, and decreased lipogenesis in WAT (23,24). In addition, heterozygous VGF knockout mice as well as ablation of several bioactive C-terminal VGF peptides showed a decrease in body weight and adiposity, and increased energy expenditure.…”

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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Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure

Cited by 37 publications

References 102 publications

VGF: An inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

VGF: An inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

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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