VGF-Derived Peptide, TLQP-21, Regulates Food Intake and Body Weight in Siberian Hamsters

Abstract

The Siberian hamster survives winter by decreasing food intake and catabolizing abdominal fat reserves, resulting in a sustained, profound loss of body weight. VGF gene expression is photoperiodically regulated in the hypothalamus with significantly higher expression in lean Siberian hamsters. The aim of this study was to investigate the role of VGF in regulating these seasonal cycles by determining the effects of a VGF-derived peptide (TLQP-21) on food intake and body weight. Acute intracerebroventricular administration of TLQP-21 decreased food intake, and chronic treatment caused a sustained reduction in food intake and body weight and decreased abdominal fat depots. Behavioral analysis revealed that TLQP-21 reduced meal size but not the frequency of feeding bouts, suggesting a primary action on satiety. Hamsters treated with TLQP-21 lost a similar amount of weight as a pair-fed group in which food intake was matched to that of the TLQP-21-treated group. Central or peripheral treatment with TLQP-21 did not produce a significant effect on resting metabolic rate. We conclude that the primary action of TLQP-21 is to decrease food intake rather than increase energy expenditure. TLQP-21 treatment caused a decrease in UCP-1 mRNA in brown adipose tissue, but hypothalamic expression of orexigenic and anorexigenic neuropeptide genes remained unchanged after TLQP-21 treatment, although compensatory increases in NPY and AgRP mRNA were observed in the pair-fed hamsters. The effects of TLQP-21 administration are similar to those in hamsters in short days, suggesting that increased VGF activity may contribute to the hypophagia that underlies the seasonal catabolic state.

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

“…This study confirms our previous report [7] but partially contrasts the findings by Jethwa et al [37] who showed that daily icv injection of TLQP-21 exerted a catabolic effect in the Siberian hamster which was associated with decreased body and WAT weight and was dependent on reduced food intake but not on increased energy expenditure. Therefore, three independent studies [7,37]; present study) evidence a catabolic role for TLQP-21, but differ in the possible mechanism underlying the effect observed: (1) increased energy expenditure/WAT catabolic effects in our studies; (2) reduced food intake in the hamster studies. A number of methodological (repeated injections vs. chronic infusion; the dose used etc.)…”

“…The lack of increase in adipose tissue is the more likely explanation for hormonal findings, i.e., the lack of increase in leptin and the decrease in ghrelin, which were evident instead in HFD-aCSF mice [47,56,69]. This study confirms our previous report [7] but partially contrasts the findings by Jethwa et al [37] who showed that daily icv injection of TLQP-21 exerted a catabolic effect in the Siberian hamster which was associated with decreased body and WAT weight and was dependent on reduced food intake but not on increased energy expenditure. Therefore, three independent studies [7,37]; present study) evidence a catabolic role for TLQP-21, but differ in the possible mechanism underlying the effect observed: (1) increased energy expenditure/WAT catabolic effects in our studies; (2) reduced food intake in the hamster studies.…”

“…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. A later study by Jethwa et al [36,37] demonstrated in hamster an anorectic effect exerted by TLQP-21 which determined a decrease in body weight and adipose fat mass.…”

“…Upon processing by the neuroendocrine-specific prohormone convertases PC1/3 and PC2, VGF may yield a number of peptides that are stored in dense core granules and secreted through regulated pathways [66]. Up to now, six VGFpeptides were shown to modulate with a remarkable peptide-specific selectivity, a diverse range of biological functions such as synaptic plasticity, apoptosis, sexual antidepressant-like behavior and inflammatory pain [2,7,10,11,35,37,58,63,64,65,70].…”

“…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.…”