ABSTRACT
Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced by neurons of the lateral hypothalamic area (LHA). Because genetic MCH deficiency induces hypophagia and loss of body fat, we hypothesized that MCH neurons may represent a specific LHA pathway that, when inhibited, contributes to the pathogenesis of certain anorexia syndromes. To test this hypothesis, we measured behavioral, hormonal, and hypothalamic neuropeptide responses in two models of hyperestrogenemia in male rats, a highly reproducible anorexia paradigm. Whereas estrogen-induced weight loss engaged multiple systems that normally favor recovery of lost weight, the expected increase of MCH mRNA expression induced by energy restriction was selectively and completely abolished. These findings identify MCH neurons as specific targets of estrogen action and suggest that inhibition of these neurons may contribute to the hypophagic effect of estrogen.
Subject(s)
Anorexia/metabolism , Estrogens/metabolism , Hypothalamic Hormones/metabolism , Hypothalamus/metabolism , Leydig Cell Tumor/metabolism , Melanins/metabolism , Pituitary Hormones/metabolism , Weight Loss/physiology , Agouti-Related Protein , Animals , Anorexia/chemically induced , Corticotropin-Releasing Hormone/genetics , Corticotropin-Releasing Hormone/metabolism , Disease Models, Animal , Drug Implants , Eating/drug effects , Energy Metabolism/drug effects , Energy Metabolism/physiology , Hormones/blood , Hypothalamus/drug effects , Intercellular Signaling Peptides and Proteins , Male , Neoplasm Transplantation , Neuropeptide Y/genetics , Neuropeptide Y/metabolism , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , Proteins/genetics , Proteins/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Weight Loss/drug effectsABSTRACT
Gonadal steroids influence food intake and body weight. Although the specific mechanisms underlying these effects are not clear, a consideration of their effects in the context of current models of energy homeostasis may ultimately lead to the identification of these mechanisms. When compared with leptin, the prototypical humoral signal of energy balance, sex steroids share many common properties related to food intake and body weight. Specifically, gonadal steroids circulate in proportion to fat mass and current energy balance, and administration of these compounds influences food intake, energy expenditure, body weight, and body composition. Moreover, both estrogens and androgens modulate central nervous system effectors of energy homeostasis that are targets for the action of leptin, including pathways that contain neuropeptide Y, pro-opiomelanocortin, or melanin-concentrating hormone. Sex steroids and leptin also regulate one another's production. Although gonadal steroids, unlike leptin, are clearly not critical to the maintenance of normal energy homeostasis, they do appear to function as physiologic modulators of this process. Identifying the specific central mediators of their effects will contribute to our understanding of their role in energy homeostasis.
Subject(s)
Energy Metabolism/physiology , Gonadal Steroid Hormones/physiology , Gonads/metabolism , Homeostasis , Leptin/physiology , Steroids/physiology , Body Weight , Eating/drug effects , Energy Metabolism/drug effects , Gonadal Steroid Hormones/pharmacology , Humans , Leptin/pharmacology , Steroids/pharmacologyABSTRACT
OBJECTIVE: To evaluate proton magnetic resonance spectroscopy (MRS) as a tool for the non-invasive assessment of murine body composition. DESIGN: Twenty C57/BL6 male mice with a wide range of body adiposities underwent both pre- and post-mortem whole-body MRS to assess body composition. MRS measures were compared to the results obtained by chemical carcass analysis, the current 'gold standard' for determination of body composition. MEASUREMENTS: Areas under the curve (AUC) for lipid and water peaks of whole body MRS spectra (AUClipid and AUCH2O, respectively) were used to determine percentages of body fat (%FATMRS) and fat free mass by MRS (%FFMMRS). Total body fat, total body water, fat free mass, and total lean mass were determined by chloroform/methanol extraction of lipid from dessicated whole carcass and compared to MRS measures (%FATMRS, %FFMMRS, AUClipid, and AUCH2O). The variability of the MRS technique was assessed by determining the coefficients of variation (COV) associated with %FATMRS, AUClipid, and AUCH2O for mice of three different adiposities. RESULTS: %FATMRS in live mice was highly correlated with body fat percentage (r=0.994, P<0.001) and total body fat (r=0.980, P<0.001) derived from chemical carcass analysis over a broad range of adiposities (7-48% body fat content by carcass analysis). There was no difference in %FATMRS measured pre- vs post-mortem (r=1.00, P<0.001). AUClipid was highly correlated with chemically derived total fat mass (r=0.996, P<0.001) and body fat percentage (r=0.981, P<0.001), while %FFMMRS was strongly correlated to chemical determinations of percentage body water (r=0.994, P<0. 001), percentage fat free mass (r=0.993, P<0.001), and percentage lean mass (r=0.792, P<0.001). AUCH2O was strongly associated with carcass analysis determinations of total body water (r=0.964, P<0. 001), total fat free mass (r=0.953, P<0.001), and total lean mass (r=0.89, P<0.001). In mice of 6%, 12%, and 43% body fat, COVs determined for %FATMRS and AUClipid were less than 10%. The COVs for AUCH2O were less than 2%. CONCLUSIONS: MRS provides precise, accurate, rapid, and non-invasive measures of body fat, body water, fat free mass, and lean mass in living mice with a broad range of adiposities.
