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

Abstract

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.

Characterization of the Reproductive Effects of the <b><i>Vgf</i></b>-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

“…However, despite such an orexigenic response, these animals did not present an increase in body weight. These data suggest a net catabolic action of this peptide and are in good agreement with previous results obtained in mice showing that TLQP-21 increased lipolysis in adipocytes in vitro [14], while chronic ICV administration of TLQP-21 (15 μg/mouse/24 h) increased energy expenditure and prevented the early phase of diet-induced obesity [9,11]. Moreover, chronic peripheral administration of TLQP-21 (40 and 400 μg/mouse/24 h) dose dependently has been reported to decrease the diameter of adipocytes in white adipose tissue in two models of obesity [14].…”

“…These observations were later confirmed by a large series of studies in Siberian hamsters and mice [2,9,10,11,12,13,14]. Thereafter, different experimental studies proposed that these peptides were also involved in the control of gastrointestinal function, water balance, endocrine and exocrine pancreatic secretion, neural and pancreatic islet β-cell survival, inflammatory pain, stress responses and emotional behavior [15,16,17,18,19,20,21,22,23].…”

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

“…The latter observation is confirmed by experiments in mice fed a high-fat diet, and selected for fast weight gain. In such animals, chronic intracerebroventricular infusion of TLQP-21 prevented the early phase of diet-induced obesity, despite overfeeding (Bartolomucci et al, 2009). At the same time, catabolic pathways within the epididimal white fat tissue were stimulated, thus supporting a role for TLQP-21 as a catabolic neuropeptide (ibidem).…”

“…Surprisingly, however, intracerebroventricular injection of the naturally occurring VGF-derived TLQP-21 peptide itself increased energy expenditure, circulating adrenalin and body temperature, and prevented diet induced obesity in mice (Bartolomucci et al, 2006(Bartolomucci et al, , 2009, while reducing food intake in Siberian hamster (Jethwa et al, 2007). Recently, the NERP-2 peptide has been shown to increase feeding, but also body temperature and oxygen consumption (Toshinai et al, 2010).…”

Identification of the C3a Receptor (C3AR1) as the Target of the VGF-derived Peptide TLQP-21 in Rodent Cells

“…Among the many peptides studied after this initial observation, TLQP-21 attracted particular attention (3)(4)(5). Indeed, intracerebroventricular injection of this peptide induces an increase in resting energy expenditure (3) and prevents high-fat diet-induced weight gain (6). This peptide increases amylase release by rat isolated pancreatic lobule and acinar cells (7).…”