The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected?

Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis. Rodent studies have shown that the ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest among pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status affects reproductive physiology and behaviours, thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails the integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged, giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems that regulate energy balance and reproductive function. Hence, this review focuses on published evidence concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homoeostasis with the neuroendocrine reproductive axis and, if so, by what means has received limited coverage in the literature; evidence to date and current theories are summarised herein.

High-Intensity Exercise Decreases IP6K1 Muscle Content and Improves Insulin Sensitivity (SI2*) in Glucose-Intolerant Individuals.

Context: Insulin resistance (IR) in skeletal muscle contributes to whole body hyperglycemia and the secondary complications associated with type 2 diabetes. Inositol hexakisphosphate kinase-1 (IP6K1) may inhibit insulin-stimulated glucose transport in this tissue type. Objective: Muscle and plasma IP6K1 were correlated with two-compartment models of glucose control in insulin-resistant hyperinsulinemic individuals. Muscle IP6K1 was also compared after two different exercise trials. Design: Nine prediabetic [hemoglobin A1c; 6.1% (0.2%)] patients were recruited to take part in a resting control, a continuous exercise (90% of lactate threshold), and a high-intensity exercise trial (6 30-second sprints). Muscle biopsies were drawn before and after each 60-minute trial. A labeled ([6,62H2]glucose) intravenous glucose tolerance test was performed immediately after the second muscle sample. Results: Fasting muscle IP6K1 content did not correlate with insulin sensitivity (SI2*) (P = 0.961). High-intensity exercise reduced IP6K1 muscle protein and messenger RNA expression (P = 0.001). There was no effect on protein IP6K1 content after continuous exercise. Akt308 phosphorylation of was significantly greater after high-intensity exercise. Intermittent exercise reduced hepatic glucose production after the same trial. The same intervention also increased SI2*, and this effect was significantly greater compared with the effect of continuous exercise improvements. Our in vitro experiment demonstrated that the chemical inhibition of IP6K1 increased insulin signaling in C2C12 myotubes. Conclusions: The in vivo and in vitro approaches used in the current study suggest that a decrease in muscle IP6K1 may be linked to whole body increases in SI2*. In addition, high-intensity exercise reduces hepatic glucose production in insulin-resistant individuals.

A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition-Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India.

PURPOSE: Advanced cancer patients with disease progression develop cachexia. Nevertheless, cancer patients at nutritional risk have shown improved body weight and quality of life with oral nutritional supplements. METHOD: This was a randomized controlled trial in adult female cancer patients (n = 63) attending palliative clinics, with symptoms of cachexia. Eligible patients were randomly distributed into control (n = 33) and intervention (n = 30) groups. Both groups were provided with nutritional and physical activity counseling, but the intervention group received an additional 100 g of Improved Atta (IAtta) for 6 months daily consumption. This study was designed to assess the efficacy of IAtta (with counseling) in enhancing the health status of cachexic patients. Anthropometric measurements, dietary intake, physical activity level and quality of life parameters were assessed at baseline, after 3 months, and at the end of 6 months. RESULTS: Patients in the control group (n = 15) had significantly decreased body weight ( P = .003), mid-upper-arm circumference ( P = .002), and body fat ( P = .002) by the end of intervention. A trend of body weight gain in the intervention group (n = 17; P = .08) and significant increase of body fat ( P = .002) was observed; moreover, patients reported a significant improvement in fatigue ( P = .002) and appetite scores ( P = .006) under quality-of-life domains at the end of intervention. CONCLUSIONS: Embedding a nutrition-sensitive intervention ( IAtta ) within Indian palliative care therapy may improve quality of life and stabilize body weight in cancer cachexia patients.