Figure 2. Schematic representation of presented pathways and proposed mechanisms.

Adipocytes, myocytes and osteoblasts are derived from mesenchymal stem cells, whereas osteoclasts and macrophages are derived from hematopoietic stem cells. Inflammatory cytokines (e.g. Interleukin 6 [IL-6] and tumor necrosis factor-alpha [TNF-α]) originate from obese adipocytes, myocytes, and macrophages.

Weight loss results in decreased inflammatory cytokines, leptin, and increased adiponectin which lead to improved metabolic profile. Exercise/muscle contraction results in decreased muscle catabolism through decreased toll-like receptor 4 (TLR-4) and inflammatory cytokines, and increased muscle anabolism through increased mechano growth factor (MGF). Exercise also exerts positive impact on bone mineral density through increased bone formation/decreased bone resorption via mechanical loading. Sclerostin increases in response to unloading by weight loss resulting in decreased bone formation through the Wnt and NF-kB pathways, an effect prevented by exercise. Thus, exercise attenuates the weight loss-induced reduction of muscle and bone mass and lifestyle therapy (weight loss + regular exercise) significantly improves physical function and metabolic profile in obese older adults.