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Role of the Cytokine-like Hormone Leptin in Musclebone Crosstalk with Aging
Mark W. Hamrick 대한골대사학회 2017 대한골대사학회지 Vol.24 No.1
The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis. Bone marrow adipogenesis is associated with low bone mass in humans and rodents, and leptin can reduce marrow adipogenesis centrally through its receptors in the hypothalamus as well as directly via its receptors in bone marrow stem cells. Yet, central leptin resistance can increase with age, and low circulating levels of leptin have been observed among the frail elderly. Thus, aging appears to significantly alter leptinmediated crosstalk among various organs and tissues. Aging is associated with bone loss and muscle atrophy, contributing to frailty, postural instability, and the incidence of falls. Therapeutic interventions such as protein and amino acid supplementation that can increase muscle mass and muscle-derived leptin may have multiple benefits for the elderly that can potentially reduce the incidence of falls and fractures.
Preventing Bone Loss and Weight Gain with Combinations of Vitamin D and Phytochemicals
Ching-Yi Lai,Jeong-Yeh Yang,Srujana Rayalam,Mary Anne Della-Fera,Suresh Ambati,Richard D. Lewis,Mark W. Hamrick,Diane L. Hartzell,Clifton A. Baile 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.11
Vitamin D and certain natural compounds have been shown to regulate both lipid metabolism and bone formation. Treatments that prevent or reverse age-related increase in bone marrow adiposity could both increase new bone formation and inhibit bone destruction. We tested the hypothesis that dietary supplementation with combinations of vitamin D and phytochemicals inhibits bone loss and decreases adiposity to a greater extent than control or vitamin D–alone diets. Aged ovariectomized female rats (12 months old, n=50, initial body weight=240 g) were given control (AIN-93M diet), vitamin D (2,400 IU/kg), or vitamin D plus resveratrol (16, 80, or 400 mg/kg of diet [low, medium, and high dose, respectively]), quercetin (80, 400, or 2,000 mg/kg of diet), and genistein (64, 256, or 1,040 mg/kg of diet) for 8 weeks. The high-dose treatment (vitamin D+400 mg/kg resveratrol+2,000 mg/kg quercetin+1,040 mg/kg genistein) reduced body weight gain (P<.05) and the fat pad weights (P<.05). This treatment also increased the serum concentration of insulin-like growth factor-1 (P<.05) and the bone mineral content of the femur. Micro-computed tomography and histomorphometric analyses indicated that the high-dose treatment prevented loss of trabecular bone (P<.05) and reduced marrow adipocytes (P<.001) and osteoclasts (P<.05) compared with the control and vitamin D alone (P<.05). We conclude that aged ovariectomized female rats supplemented with vitamin D combined with genistein, quercetin, and resveratrol had improved bone mineral density and reduced body weight gain and a significant decrease in bone marrow adipocytes. The synergistic effects of a combination of phytochemicals with vitamin D may be effective in reducing bone loss and weight gain after menopause.