INS and obesity due to melanocortin 4 receptor deficiency: Although we could not infer any causal relationships between these altered metabolic profiles and obesity from the meta-analysis, the results helped to generate novel hypothesis to be tested in our dietary restriction trial in mice, which demonstrated that restriction of BCAAs within a HFD could prevent the development of obesity, adipose inflammation, elevation in serum glucose and insulin levels, and insulin resistance induced by HFD, providing a promising strategy to mitigate diet-induced obesity.