Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice.
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 weight-gaining 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 beta3-adrenergic receptor mRNA. Peroxisome-proliferator-activated-receptor-delta 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.
Bartolomucci
Alessandro
A
Institute of Neuroscience, CNR, Via del Fosso di Fiorano, 64/65, 00143, Rome, Italy, alessandro.bartolomucci@unipr.it.
Bresciani
Elena
E
Bulgarelli
Ilaria
I
Rigamonti
Antonello E
AE
Pascucci
Tiziana
T
Levi
Andrea
A
Possenti
Roberta
R
Torsello
Antonio
A
Locatelli
Vittorio
V
Muller
Eugenio E
EE
Moles
Anna
A