Purple sweet potato (Ipomoea batatas L. Lam) leaves extract prevents weight gain and lipotoxicity in mice fed a high-fat diet by increasing metabolic flexibility and oxidative metabolism in skeletal muscle and brown adipose tissue

Purple sweet potato leaves are a rich source of caffeoylquinic acids (CQA) and related compounds with potential metabolic benefits. Our previous research demonstrated that 5-CQA and 3,4-diCQA increase mitochondrial respiration in primary hepatocytes. To explore the translational relevance of purple sweet potato leaves extract (PSPLE) in the management and treatment of obesity, we evaluated the effect of PSPLE in C57BL/6 mice fed a high-fat (HF) diet supplemented with either 1% or 3% PSPLE (w/w) and assessed insulin secretion in INS-1E cells. PSPLE phenolic compounds were identified by LC-MS. Male C57BL/6J mice were fed (1) a Control, (2) high-fat (HF) diet, (3) HF diet supplemented with 1% and (4) HF diet supplemented with 3% of PSPLE for 15 weeks. Body composition, energy expenditure, glucose and insulin tolerance, serum metabolites, and tissue morphology were evaluated. AMPK activation was analyzed in the liver and skeletal muscle. Complementary, β-cell function was assessed in vitro. LC–MS revealed that PSPLE contained abundant CQA derivatives (5-CQA, caffeic acid, 3,4-di-CQA, 3,5-di-CQA, 4,5-di-CQA, 4 F-5CQA, and 3,4,5-tri-CQA). The HF + 1% PSPLE diet attenuated weight gain and adipocyte hypertrophy, increased brown adipose UCP-1 expression, and prevented hepatic steatosis. AMPK phosphorylation was enhanced in the liver and muscle, paralleling higher oxygen consumption and energy expenditure. Although PSPLE stimulated β-cell metabolism and insulin secretion in vitro, in vivo glucose tolerance showed only modest improvement, likely reflecting the multiple regulatory inputs on insulin secretion under physiological conditions. PSPLE enhanced metabolic flexibility and oxidative capacity in HF-fed mice by activating AMPK-dependent pathways in muscle, liver, and adipose tissue. The higher efficacy of the 1% PSPLE indicates a hormetic response, where low polyphenol exposure triggers adaptive mitochondrial and metabolic activation, on the contrary, higher doses offer no further benefits. These results present PSPLE as a sustainable, polyphenol-rich food ingredient with potential to combat obesity-related metabolic dysfunction.