Phytocompounds That Target White Adipose Tissue for Weight Loss: A Review Spanning From Ucp1 Induction in Rodents to Human Clinical Trials.

Most drugs and supplements for weight loss decrease appetite and food intake, resulting in loss of lean mass and fat mass. An ideal strategy for weight loss would be to directly target adipocytes and stimulate mitochondrial thermogenesis fueled by fatty acid oxidation. Many phytocompounds and food components can act directly on rodent adipocytes to stimulate expression of Ucp1, a mitochondrial protein and marker for thermogenic capacity. Expression of Ucp1 is highly inducible in rodent adipocytes and correlates with lower adiposity after high-fat diet consumption. The aim of this review is to determine whether the natural compounds that stimulate expression of rodent Ucp1 have the same effect in human adipocytes and translate to reduction of body weight in human clinical trials. Sixteen natural compounds that induce Ucp1 expression in rodent primary adipocytes or adipose tissue were identified from literature searches of PubMed and Web of Science databases. Of these, resveratrol, naringenin, curcumin, menthol, genistein, and artepillin C induce UCP1 in human adipocytes. The most active phytocompounds in human adipocytes bypass receptor signaling and bind nuclear receptors that act on promoter elements to induce thermogenesis genes. Resveratrol, naringenin, curcumin, epigallocatechin-3-gallate, fucoxanthin, menthol, provitamin A carotenoids, and capsaicin have been evaluated in clinical trials for weight loss. Naringenin and curcumin stimulate weight loss in multiple clinical trials. Extracts enriched in the active component stimulate greater clinical weight loss than any single active component. We conclude that specific natural compounds that target adipose tissue can stimulate human energy expenditure and meaningful weight loss.