Effects of alpha-melanocyte-stimulating hormone on mitochondrial energy metabolism in rats of different age-groups.
Hypothalamic alpha-melanocyte-stimulating hormone (α-MSH) is a key catabolic mediator of energy homeostasis. Its anorexigenic and hypermetabolic effects show characteristic age-related alterations that may be part of the mechanism of middle-aged obesity and geriatric anorexia/cachexia seen in humans and other mammals. We aimed to investigate the role of α-MSH in mitochondrial energy metabolism during the course of aging in a rodent model. To determine the role of α-MSH in mitochondrial energy metabolism in muscle, we administered intracerebroventricular (ICV) infusions of α-MSH for 7-days to different age-groups of male Wistar rats. The activities of oxidative phosphorylation complexes I to V and citrate synthase were determined and compared to those of age-matched controls. We also quantified mitochondrial DNA (mtDNA) copy number and measured the expression of the master regulators of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPARγ). The peptide reduced weight gain in juvenile rats to one fifth of that of controls and increased the weight loss in older animals by about five fold. Mitochondrial DNA copy number inversely correlated with changes in body weight in controls, but not in α-MSH-treated animals. The strong increase in body weight in young rats was associated with a low mtDNA copy number and high PPARγ mRNA levels in controls. Expression of PGC-1α and PPARγ declined with age, whereas OXPHOS and citrate synthase enzyme activities were unchanged. In contrast, α-MSH treatment suppressed OXPHOS enzyme and citrate synthase activity. In conclusion, our results showed age-related differences in the metabolic effects of α-MSH. In addition, administration of α-MSH suppressed citrate synthase and OXPHOS activities independent of age. These findings suggest that α-MSH exposure may inhibit mitochondrial biogenesis.
Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
René G
RG
Feichtinger
Institute for Translational Medicine, Medical School, University of Pécs, Hungary.
Erika
E
Pétervári
Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
Michaela
M
Zopf
Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
Silvia
S
Vidali
Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
Sepideh
S
Aminzadeh-Gohari
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
Johannes A
JA
Mayr
Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria. Electronic address: b.kofler@salk.at.
Barbara
B
Kofler
Institute for Translational Medicine, Medical School, University of Pécs, Hungary.
Márta
M
Balaskó
D000375:Aging; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D017208:Rats, Wistar; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism*
D047495:PPAR gamma; D011979:Receptors, Pituitary Hormone; D014157:Transcription Factors; D000521:alpha-MSH; C029446:MSH receptor
Aging; Mitochondria; Muscle; Obesity; Oxidative phosphorylation; α-MSH