kiss1-protein--human and Obesity--Morbid

Body energy balance and metabolic signals are important modulators of puberty and reproductive function, so that perturbations of metabolism and energy reserves (ranging from persistent energy insufficiency to morbid obesity) are frequently linked to reproductive disorders. The mechanisms for the tight association between body metabolic state and reproduction are multifaceted, and likely involve numerous peripheral hormones and central transmitters. In recent years, a prominent role of kisspeptins in the central pathways responsible for conveying metabolic information into the brain centers responsible for reproductive control, and specifically GnRH neurons, has been proposed on the basis of a wealth of expression and functional data. In this chapter, we will summarize such evidence, with special attention to the potential (direct and/or indirect) interaction of leptin and kisspeptin pathways. In addition, other potential metabolic modulators of kisspeptin signaling, as well as some of the putative molecular mechanisms for the metabolic regulation of Kiss1 will be briefly reviewed. Conflictive data, including those questioning an essential role of Kiss1 neurons in mediating leptin effects on the reproductive axis, will be also discussed. All in all, we aim to provide an integral and balanced view of the physiological relevance and potential mechanisms for the metabolic control of the kisspeptin system, as important pathway for the integral regulation of energy balance, puberty onset, and fertility.

Topics: Animals; Brain; Energy Metabolism; Fertility; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Leptin; Neurons; Obesity, Morbid; Puberty; Reproduction; Signal Transduction

Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery.

Topics: Adolescent; Adult; Anastomosis, Roux-en-Y; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Humans; Insulin; Kisspeptins; Liver; Male; Middle Aged; Obesity, Morbid; Treatment Outcome; Young Adult

Obesity is a metabolic disease with a serious health burden in children and adults, and it induces a variety of conditions including subfecundity. Sleeve gastrectomy showed encouraging results in terms of weight loss and improve quality of life, and this study aimed to determine whether sleeve gastrectomy could reverse obesity-induced impaired fertility in male Sprague-Dawley rats.. After 16 weeks of a chow diet (CD) or a high-fat diet (HFD) challenge, rats on the HFD were given a sleeve gastrectomy or sham operation and then fed an HFD for another 8 weeks. Serum glucose, insulin, lipids, sex hormone, sperm quality, inflammatory profile of the testis, and hypothalamic Kiss1 expression in the three study groups were compared.. Sleeve gastrectomy significantly decreased HFD-induced obesity and serum glucose and insulin levels. It also reversed the HFD-induced increase in teratozoospermia and decreases in sperm motility and progressive motility. Testicular morphological abnormalities were also improved after sleeve gastrectomy. Enzyme-linked immunosorbent assay showed that the expression of sex hormones increased after sleeve gastrectomy and that expression of inflammatory factors decreased. The HFD induced a hypothalamic inflammatory response that inhibited Kiss1 expression, which in turn mediated sex hormone expression. Sleeve gastrectomy treatment improved the hypothalamic response.. The results consistently showed that sleeve gastrectomy reversed obesity-induced male fertility impairment by decreasing the inflammatory responses of the testis and hypothalamus.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Gastrectomy; Humans; Hypogonadism; Hypothalamus; Insulin; Kisspeptins; Male; Obesity; Obesity, Morbid; Quality of Life; Rats; Rats, Sprague-Dawley; Sperm Motility; Testis; Weight Loss