Aims: Both the neuronal--derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co--ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. Methods: To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. Results: PYY−/− mice exhibited increased fasting--induced food intake, enhanced fasting and oral glucose--induced serum insulin levels, and an impaired insulin tolerance, − changes not observed in NPY−/− mice. Interestingly, whereas PYY deficiency--induced impairment in insulin tolerance remained in NPY−/−PYY−/− mice, effects of PYY deficiency on fasting--induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY−/−PYY−/− mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting--induced hyperphagia. Moreover, NPY−/−PYY−/−, but not NPY−/− or PYY−/− mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY−/− and PYY−/− mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY−/−PYY−/− mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. Conclusions: These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis. INTRODUCTION A complex picture has emerged as to the regulation of energy balance and glucose homeostasis in mammals, which involve co--ordinated actions from neuronal factors

No abstract

Objective: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. Methods: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. Results: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. Conclusions: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

No abstract