Data gleaned recently shows that ghrelin, a stomach derived peptide, and liver-expressed-antimicrobial peptide 2 (LEAP-2) play opposite roles on food intake. However, the data available with LEAP-2 in relation to in vivo studies are still very scanty and some key questions regarding the interplay among ghrelin and LEAP-2 remain to be answered. In this work, using rats and mice, we study fasting-induced food intake as well as testing the effect of diet exposure, e.g., standard diet and high fat diet, in terms of ghrelin-induced food intake. The anorexigenic effect of LEAP-2 on fasting induced food intake appears to be dependent on energy stores, being more evident in ob/ob than in wild type mice and also in animals exposed to high fat diet. On the other hand, LEAP-2 administration markedly inhibited ghrelin-induced food intake in lean, obese (ob/ob and DIO) mice, aged rats and GH-deficient dwarf rats. In contrast, the inhibitory effect on glucose levels can only be observed in some specific experimental models indicating that the mechanisms involved are likely to be quite different. Taken together from these data, LEAP-2 emerged as a potential candidate to be therapeutically useful in obesity.

Chemerin (also known as tazarotene-induced gene 2 and retinoic acid receptor responder 2) has been identified as an adipokine that exerts effects on many biological processes, including adipogenesis, angiogenesis, inflammation, immune responses, and food intake. This variety of effects has led to its implication in obesity and co-morbidities including diabetes and a risk of cardiovascular disease. The biological effects are mostly mediated by a so-called G protein-coupled receptor, chemokine-like receptor 1 (CMKLR1). Given the association of chemerin with obesity and related diseases, we decided to study in detail the regulation of chemerin and CMKLR1 expression in white adipose tissue (WAT). Specifically, we focused on their expression levels in physiological and pathophysiological settings involved in energy balance: e.g., fasting, postnatal development, and gender. We used Sprague Dawley rats with different nutritional statuses, levels of hormonal deficiency, and states of development as well as ob/ob (leptin-deficient) mice. We analysed the protein expression of both the ligand and receptor (chemerin and CMKLR1) in gonadal WAT by western blotting. We found that chemerin and CMKLR1 protein levels were regulated in WAT by different conditions associated with metabolic changes such as nutritional status, sex steroids, pregnancy, and food composition. Our data indicate that regulation of the expression of this new adipokine and its receptor by nutritional status and gonadal hormones may be a part of the adaptive mechanisms related to altered fat mass and its metabolic complications.