alarin and Body-Weight

Hypothalamic neuropeptides influence the main components of energy balance: metabolic rate, food intake, body weight as well as body temperature, by exerting either an overall anabolic or catabolic effect. The contribution of alarin, the most recently discovered member of the galanin peptide family to the regulation of energy metabolism has been suggested. Our aim was to analyze the complex thermoregulatory and food intake-related effects of alarin in rats. Adult male Wistar rats received different doses of alarin (0.3; 1; 3 and 15μg corresponding approximately to 0.1, 0.33, 1, and 5 nmol, respectively) intracerebroventricularly. Regarding thermoregulatory analysis, oxygen consumption (indicating metabolic rate), core temperature and heat loss (assessed by tail skin temperature) were recorded in an Oxymax indirect calorimeter system complemented with thermocouples and Benchtop thermometer. In order to investigate potential prostaglandin-mediated mechanisms of the hyperthermic effect of alarin, effects of intraperitoneally applied non-selective (indomethacin, 2mg/kg) or selective cyclooxygenase inhibitor (COX-2 inhibitor meloxicam, 1; 2mg/kg) were tested. Effects of alarin on daytime and nighttime spontaneous food intake, as well as, 24-h fasting-induced re-feeding were recorded in an automated FeedScale system. Alarin increased oxygen consumption with simultaneous suppression of heat loss leading to a slow coordinated rise in core temperature. Both applied COX-inhibitors suppressed this action. Alarin failed to induce daytime food intake, but suppressed spontaneous nighttime and also fasting-induced re-feeding food intake. Alarin appears to elicit a slow anorexigenic and prostaglandin-mediated, fever-like hyperthermic response in rats. Such a combination would characterize a catabolic mediator. The potential involvement of alarin in sickness behavior may be assumed.

Topics: Animals; Body Temperature; Body Temperature Regulation; Body Weight; Eating; Energy Metabolism; Galanin; Galanin-Like Peptide; Homeostasis; Injections, Intraventricular; Male; Neuropeptides; Rats, Wistar

In order to investigate the central effect of alarin on glucose uptake, we administered alarin and/ or its inhibitor, ala6-25Cys into the cerebral ventricles of the type 2 diabetic rats. Then the relative parameters about glucose uptake in skeletal muscles were measured. We found that central treatment with alarin significantly increased the food intake, body weight and glucose infusion rates in hyperinsulinemic euglycemic clamp tests of the animals. Besides, the treatment also enhanced 2-deoxy-[3H]-D-glucose uptake, vesicle-associated membrane protein 2 contents, glucose transporter 4 protein and mRNA expression, as well as pAktThr308, pAktSer473 and total Akt levels in muscle cells, but reduced plasma glucose and insulin levels of the rats. All of the alarin-inducing events may be antagonised by central injection of ala6-25Cys. These results suggest that central administration of alarin stimulates glucose uptake mediated by activation of Akt signal pathway in type 2 diabetic animals.

Topics: Animals; Body Weight; Cell Line; Diabetes Mellitus, Experimental; Eating; Galanin-Like Peptide; Glucose; Glucose Transporter Type 4; Injections, Intraventricular; Insulin; Mice; Muscle, Skeletal; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats

Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism. Our previous studies had found that galanin might facilitate insulin sensitivity via activation of its central receptors. To date, little is known about whether central alarin may exert similar effects on insulin sensitivity. In order to investigate this, alarin and its specific antagonist, alarin 6-25Cys, were administered into the cerebral ventricles of type 2 diabetic rats (T2DR) to evaluate the changes in insulin resistance. The results indicated that central treatment with alarin significantly increased the body weight of animals, the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as glucose transporter 4 (GLUT4 (SLC2A4)) protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels. These effects of alarin may be inhibited by pretreatment with alarin 6-25Cys. The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in T2DR.

Topics: 4-Chloro-7-nitrobenzofurazan; Adipocytes; Adiponectin; Animals; Blood Glucose; Blotting, Western; Body Weight; Cell Membrane; Deoxyglucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Galanin-Like Peptide; Gene Expression; Glucose Transporter Type 4; Injections, Intraventricular; Insulin Resistance; Male; Peptide Fragments; Protein Transport; Rats, Wistar; Retinol-Binding Proteins, Plasma; Reverse Transcriptase Polymerase Chain Reaction; Vesicle-Associated Membrane Protein 2

Previous data from our labs and from others have demonstrated that intracerebroventricular (ICV) injection of alarin has orexigenic activity and significantly increases plasma luteinizing hormone (LH) secretion in a gonadotropin-releasing hormone (GnRH) dependent manner. The purpose of the current experiments was to determine if the amino acids at the amino-terminal end of the alarin peptide are critical for alarin's effects on reproductive and feeding systems. First, we injected male mice ICV with full-length alarin (Ala1-25) or peptide fragments missing residues at the amino-terminal end (Ala3-25 or Ala6-25 Cys). Neither peptide fragment alone, significantly increased food intake in male mice compared to controls. Second, ICV injection of Ala1-25, but not Ala3-25, significantly (p < 0.01) increased GnRH-mediated LH secretion. Surprisingly, Ala6-25 Cys significantly (p < 0.05) inhibited plasma LH secretion and inhibited Ala1-25 actions. In conclusion, elimination of the first five amino acids of alarin not only abolishes the biological activity of alarin, but becomes an antagonist to alarin-specific effects. Furthermore, Ala6-25 Cys seems to act as a specific antagonist to putative alarin receptors and therefore may be an important tool in identifying alarin-specific receptors.

Topics: Animals; Body Temperature; Body Weight; Brain Chemistry; Eating; Galanin-Like Peptide; Gonadotropin-Releasing Hormone; Injections, Intraventricular; Luteinizing Hormone; Male; Mice; Mice, Inbred C57BL; Peptide Fragments; Telemetry