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At the adipose tissue level, the combined GIP and GLP-1 agonism reduces M1 macrophage infiltration and pro-inflammatory cytokines such as leptin, increases adiponectin, and enhances insulin sensitivity, thereby improving adipocyte dysfunction.39 GIP additionally increases the storage capacity of adipose tissue, which lowers the likelihood of ectopic fat deposition and reduces the extent of visceral fat.1,5,39 Furthermore, it has demonstrated neuroprotective effects and promotes bone formation1 (Table 2)

Save Tesamorelin is a synthetic analog of growth-hormone-releasing hormone (GHRH) with the strongest human evidence for reducing visceral fat 15-18% reductions in HIV-associated lipodystrophy trials (Falutz et al., NEJM 2007)

Since NEDD4 is a classical E3 ligase targeting PPAR, this modification ultimately promotes PPAR degradation and disrupts fatty acid homeostasis

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