Aims/hypothesis Orexin A (OXA) modulates body weight, food intake and energy expenditure. In vitro, OXA increases PPARγ (also known as PPARG) expression and inhibits lipolysis, suggesting direct regulation of lipid metabolism. Here, we characterise the metabolic effects and mechanisms of OXA action in adipocytes. Methods Isolated rat adipocytes and differentiated murine 3T3-L1 adipocytes were exposed to OXA in the presence or absence of phosphoinositide 3-kinase (PI3K) inhibitors. Pparγ expression was silenced using small interfering RNA. Glucose uptake, GLUT4 translocation, phosphatidylinositol (3,4,5)-trisphosphate production, lipogenesis, lipolysis, and adiponectin secretion were measured. Adiponectin plasma levels were determined in rats treated with OXA for 4 weeks.Results OXA PI3K-dependently stimulated active glucose uptake by translocating the glucose transporter GLUT4 from cytoplasm into the plasma membrane. OXA increased cellular triacylglycerol content via PI3K. Cellular triacylglycerol accumulation resulted from increased lipogenesis as well as from a decrease of lipolysis. Adiponectin levels in chow-and high-fat diet-fed rats treated chronically with OXA were increased. OXA stimulated adiponectin expression and secretion in adipocytes. Both pharmacological blockade of peroxisome proliferator-activated receptor γ (PPARγ) activity or silencing Pparγ expression prevented OXA from stimulating triacylglycerol accumulation and adiponectin production. Conclusions/interpretation Our study demonstrates that OXA stimulates glucose uptake in adipocytes and that the evolved energy is stored as lipids. OXA increases lipogenesis, inhibits lipolysis and stimulates the secretion of adiponectin. These effects are conferred via PI3K and PPARγ2. Overall, OXA's effects on lipids and adiponectin secretion resemble that of insulin sensitisers, suggesting a potential relevance of this peptide in metabolic disorders.Electronic supplementary material The online version of this article

Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m2) and obese patients (BMI>35 kg/m2). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4.48±0.19 ng/ml vs. 6.63±0.29 ng/ml; p<0.001, KISS: 1.357±0.15 nmol/l vs. 2.165±0.174 nmol/l; p<0.01). SPX negatively correlated with BMI, HOMA-IR, insulin, glucagon, active ghrelin and leptin. Positive correlations were found between SPX and QUICKI index, McAuley index, serum levels of obestatin, GLP-1 and adiponectin and orexin-A Serum KISS negatively correlated with BMI, HOMA-IR, serum levels of insulin, glucagon, active ghrelin and leptin. KISS positively correlated with QUICKI index, McAuley index and adiponectin. In summary, SPX and KISS show negative correlations with obesity, insulin resistance indices, and hormones known to affect insulin sensitivity in females. Both, SPX and KISS could be therefore relevant in the pathophysiology of obesity and insulin resistance.

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Aims/hypothesis Glucagon reduces body weight by modifying food intake, glucose/lipid metabolism and energy expenditure. All these physiological processes are also controlled by fibroblast growth factor 21 (FGF-21), a circulating hepatokine that improves the metabolic profile in obesity and type 2 diabetes. Animal experiments have suggested a possible interaction between glucagon and FGF-21 however, the metabolic consequences of this crosstalk are not understood. Methods The effects of exogenous glucagon on plasma FGF-21 levels and lipolysis were evaluated in healthy volunteers and humans with type 1 diabetes, as well as in rodents with streptozotocin (STZ)-induced insulinopenic diabetes. In vitro, the role of glucagon on FGF-21 secretion and lipolysis was studied using isolated primary rat hepatocytes and adipocytes. Fgf-21 expression in differentiated rat pre-adipocytes was suppressed by small interfering RNA and released FGF-21 was immunoneutralised by polyclonal antibodies. Results Glucagon induced lipolysis in healthy human volunteers, patients with type 1 diabetes, mice and rats with STZ-induced insulinopenic diabetes, and in adipocytes isolated from diabetic and non-diabetic animals. In addition, glucagon increased circulating FGF-21 in healthy humans and rodents, as well as in patients with type 1 diabetes, and insulinopenic rodents. Glucagon stimulated FGF-21 secretion from isolated primary hepatocytes and adipocytes derived from animals with insulinopenic diabetes. Furthermore, FGF-21 stimulated lipolysis in primary adipocytes isolated from non-diabetic and diabetic rats. Reduction of Fgf-21 expression (by approximately 66%) or immunoneutralisation of released FGF-21 markedly attenuated glucagon-stimulated lipolysis in adipocytes. Conclusions/interpretation These results indicate that glucagon increases circulating FGF-21 independently of endogenous insulin levels. FGF-21 participates in glucagon-induced stimulation of lipolysis.

This study was conducted to investigate the effect of insect full-fat meals ( Tenebrio molitor and Zophobas morio larvae), added “ on top ” of a complete diet or calculated into diets, on the growth performance, selected blood, and immune system traits of broiler chickens. 1,000 one-day-old female Ross 308 broiler chicks were used in 2 independent experiments. In the first trial, the birds were randomly assigned to 6 treatments, 10 replicate pens per treatment, and 10 birds per pen, i.e., negative control; positive control with salinomycin addition (60 mg/kg diet), and addition of 0.2% and 0.3% of T. molitor and Z. morio full-fat meals “ on top ”. In the second experiment, 4 treatments, 10 replicate pens per treatment, and 10 birds per pen were set, i.e., negative control, positive control with salinomycin addition (60 mg/kg diet), and 0.3% of T. molitor and Z. morio full-fat meals calculated in the diets. In both trials the supplementation of insects increased the BWG (Exp. 1: P = 0.024; Exp. 2: P = 0.046) and FI (Exp. 1: P = 0.022; Exp. 2: P = 0.026), and no negative effect on the FCR was recorded in experiment one ( P = 0.514), however in second trial insects addition increased FCR values ( P = 0.011). In addition, in the first trial, groups fed insects and PC comparing to NC decreased the IgY ( P = 0.045) and IgM, ( P < 0.001) levels. In the second experiment, IgM levels were also decreased ( P < 0.001) in groups fed insects comparing to NC. Moreover, in first trial the IgM levels were negatively correlated to the BWG (r = –0.4845) and FI (r = –0.4986), with statistically significant values ( P < 0.001). In conclusion, the current results confirmed that small amount addition (0.2% and 0.3%) of T. molitor and Z. morio full-fat meals to the diet of broiler chickens can improve growth performance and change selected the immune system traits.