leptin and Muscular-Diseases

During the acute training response, peripheral cellular mechanisms are mainly metabolostatic to achieve energy supply. During prolonged training, glycogen deficiency occurs; this is associated with increased expression of local cytokines, and decreased insulin secretion and beta-adrenergic stimulation and lipolysis in adipose tissue which looses energy. This is indicated by decrease of adipocyte hormone leptin, which has inhibitory effects on excitatory hypothalamic neurons. Leptin, insulin, and cytokines such as interleukin 6 (IL-6) contribute to the metabolic error signal to the hypothalamus which result in decrease of hypothalamic release hormones and sympathoadrenergic stimulation. Thyroid stimulating hormone (TSH) is correlated to the metabolic hormones leptin and insulin, and may be used as indicator of metabolic control. Because the hypothalamus integrates various error signals (metabolic, hormonal, sensory afferents, and central stimuli), the pituitary's releasing hormones represent the functional status of an athlete. Long-term overtraining will lead to downregulation of hypothalamic hormonal and sympathoadrenergic responses, catabolism, and fatigue. These changes contribute to myopathy with predominant expression of slow muscle fiber type and inadequacy in performance. Thyroid hormones are closely involved in the training response and metabolic control.

Topics: Animals; Energy Metabolism; Exercise; Humans; Hypothalamus; Insulin; Interleukin-6; Leptin; Muscular Diseases; Physical Fitness; Thyroid Hormones; Thyrotropin

Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Here we describe the phenotype of a child with CGL4 due to a rare, novel pathogenic variant in the PTRF/CAVIN1 gene and the long-term effects of metreleptin substitution on comorbidities.. We describe a now 20-year-old female patient. At the age of 14-years, she was referred to the University Clinic because of uncontrolled diabetes with an HbA1c of 9.3%, requiring 2.4 IU insulin/kg total-body-weight to normalize blood glucose, hepatomegaly, and hypertriglyceridemia of 515 mg/dL. Additionally, she was suffering from malignant cardiac arrhythmia, myopathy, and hyperCKemia. In light of these clinical findings, she was diagnosed with CGL due to a rare, novel variant in the PTRF gene, and was started on metreleptin, a synthetic analog of human leptin. After the initiation of metreleptin treatment, insulin therapy could be stopped and improvement of sonographically assessed liver size was observed, even though serum liver function test stayed mildly elevated. Furthermore, a noticeable improvement of the serum triglyceride levels was also seen. Medical care and regular follow-up visits are being carried out by a multi-disciplinary team.. Although CGL4 is rare, due to its life-threatening comorbidities and the opportunity for an early intervention, it is important that the clinicians should recognise these patients.

Topics: Arrhythmias, Cardiac; Female; Humans; Insulins; Leptin; Lipodystrophy; Lipodystrophy, Congenital Generalized; Muscular Diseases; RNA-Binding Proteins

Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/β-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL.. We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1-L4 Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients.. In this cross-sectional study, we included 11 diabetic patients with BSCL (age 24.7±8.1years; 6 females). Sclerostin, leptin, L1-L4 TBS, BMD were measured. Potential pathophysiological mechanisms have been suggested.. Mean serum sclerostin was elevated (44.7±13.4pmol/L) and was higher in men than women (55.3±9.0 vs. 35.1±8.4pmol/L, p=0.004). Median of serum leptin was low [0.9ng/mL (0.5-1.9)]. Seven out of 11 patients had normal BMD, while four patients had high bone mass (defined as Z-score>+2.5SD). Patients on insulin had lower sclerostin (37.3±9.2 vs. 52.6±13.4pmol/L, p=0.05). The mean TBS was 1.402±0.106, and it was higher than 1.300 in nine patients.. Patients with lipoatrophic diabetes (BSCL) have high serum concentrations of sclerostin, normal or high BMD, and reasonable trabecular bone mass measured by TBS. This is the first report of high sclerostin and good bone microarchitecture (TBS) in BSCL patients.

Topics: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Bone Density; Bone Morphogenetic Proteins; Cancellous Bone; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Genetic Markers; Humans; Hyperinsulinism; Hypertrophy; Insulin; Leptin; Lipodystrophy, Congenital Generalized; Male; Muscular Diseases; Young Adult

Obese phenotypes and aging are independently associated with hypothalamic-pituitary-adrenocortical (HPA) axis and leptin secretion alterations. However, leptin secretion and HPA axis function in elderly persons with other body composition phenotypes is largely unknown.. Forty-five healthy elderly participants were classified normal lean (NL), sarcopenic (SS), sarcopenic-obese (SO), or obese (OO) using dual-energy x-ray absorptiometry. Growth hormone (GH), cortisol, and leptin secretion were evaluated during a free-running night, and oral glucocorticoid suppression test (dexamethasone DEX). Diurnal cortisol secretion was assessed by hourly salivary samples with timed meals. Data were analyzed using cluster, deconvolution, and approximate entropy (ApEn) analyses.. GH area, total secretion, and mean concentration during the free-running night was lower in the SO and OO groups verses the SS and NL groups (p <.02, Wilcoxon test). GH mean concentration and total secretion significantly increased in all groups during DEX (overall p <.05) except the SO group, in which ApEn increased (p =.03). Pre- and postbreakfast peak salivary cortisol (p =.004) and area under the curve (p =.03) was greatest in the SS group. Baseline leptin (11:00 pm) was significantly higher in the SO, OO, and SS groups verses the NL group (p =.01). Appendicular skeletal muscle mass was independently and negatively correlated with leptin in all groups, even after adjusting for percentage body fat (p =.001).. In the presence of obesity, GH secretion was depressed with a blunted and disorderly response to oral glucocorticoid suppression in SO participants. Sarcopenic participants had concomitantly elevated leptin and cortisol relative to their low body fat mass. Complex or dysregulated neuroendocrine feedback systems appear to be operating in elderly persons with specific body composition phenotypes.

Topics: Aged; Aged, 80 and over; Body Composition; Female; Growth Hormone; Humans; Hydrocortisone; Leptin; Male; Muscular Diseases