INS and obesity due to melanocortin 4 receptor deficiency: ATMs-sEVs in obese (OATMs-sEVs) or non-lean individuals contain miRNA-29a, which directly targets peroxisome proliferator-activated receptors (PPAR-δ) by transferring it to fat, muscle, and liver cells, impelling glucose uptake by fat and muscle cells, promoting glucose output in response to insulin, reducing cellular and systemic insulin sensitivity, and promoting obesity-induced insulin resistance (Liu et al., 2019).