GPR10 and neuropeptide FF receptor 2 (NPFFR2) play important role in the regulation of food intake and energy homeostasis. Understanding the interaction between these receptors and their specific ligands, such as prolactin-releasing peptide, is essential for developing stable peptide analogs with potential for treating obesity. By breeding and characterizing double knockout (dKO) mice fed standard or high-fat diet (HFD), we provide insights into the metabolic regulation associated with the GPR10 and NPFFR2 deficiency. Both WT and dKO mice were subjected to behavioral tests and an oral glucose tolerance test. Moreover, dual-energy X-ray absorptiometry (DEXA) followed by indirect calorimetry were performed to characterize dKO mice. dKO mice of both sexes, when exposed to an HFD, showed reduced glucose tolerance, hyperinsulinemia, and insulin resistance compared with controls. Moreover, they displayed increased liver weight with worsened hepatic steatosis. Mice displayed significantly increased body weight, which was more pronounced in dKO males and caused by higher caloric intake on a standard diet, while dKO females displayed obesity characterized by increased white adipose tissue and enhanced hepatic lipid accumulation on an HFD. Moreover, dKO females exhibited anxiety-like behavior in the open field test. dKO mice on a standard diet had a lower respiratory quotient, with no significant changes in energy expenditure. These results provide insights into alterations associated with disrupted GPR10 and NPFFR2 signaling, contributing to the development of potential anti-obesity treatment.

• Klíčová slova
• GPR10/NPFFR2-deficient mice, double KO mice, impaired glucose utilization, insulin resistance, obesity,
• MeSH
• bílá tuková tkáň metabolismus   MeSH
• dieta s vysokým obsahem tuků * škodlivé účinky   MeSH
• energetický metabolismus genetika   MeSH
• inzulinová rezistence MeSH
• myši inbrední C57BL MeSH
• myši knockoutované * MeSH
• myši MeSH
• obezita * metabolismus   genetika   MeSH
• prediabetes * metabolismus   genetika   MeSH
• receptory neuropeptidů * genetika   metabolismus   nedostatek   MeSH
• receptory spřažené s G-proteiny * genetika   metabolismus   nedostatek   MeSH
• sexuální faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• neuropeptide FF receptor MeSH Prohlížeč
• receptory neuropeptidů * MeSH
• receptory spřažené s G-proteiny * MeSH

A previous study on neuropeptide FF receptor 2 (NPFFR2)-deficient mice has demonstrated that NPFFR2 is involved in the control of energy balance and thermogenesis. Here, we report on the metabolic impact of NPFFR2 deficiency in male and female mice that were fed either a standard diet (STD) or a high-fat diet (HFD) and each experimental group consisted of ten individuals. Both male and female NPFFR2 knockout (KO) mice exhibited severe glucose intolerance that was exacerbated by a HFD diet. In addition, reduced insulin pathway signaling proteins in NPFFR2 KO mice fed a HFD resulted in the development of hypothalamic insulin resistance. HFD feeding did not cause liver steatosis in NPFFR2 KO mice of either sex, but NPFFR2 KO male mice fed a HFD had lower body weights, white adipose tissues, and liver and lower plasma leptin levels compared with their wild-type (WT) controls. Lower liver weight in NPFFR2 KO male mice compensated for HFD-induced metabolic stress by increased liver PPARα and plasma FGF21 hepatokine, which supported fatty acid β-oxidation in the liver and white adipose tissue. Conversely, NPFFR2 deletion in female mice attenuated the expression of Adra3β and Pparγ, which inhibited lipolysis in adipose tissue.

• Klíčová slova
• glucose intolerance, high-fat diet, insulin resistance, knockout mice, neuropeptide FF,
• MeSH
• bílá tuková tkáň metabolismus   MeSH
• dieta s vysokým obsahem tuků MeSH
• glukosa metabolismus   MeSH
• inzulinová rezistence * MeSH
• játra metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• obezita metabolismus   MeSH
• porucha glukózové tolerance * metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukosa MeSH
• neuropeptide FF receptor MeSH Prohlížeč