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Obesity is closely related with insulin resistance and chronic inflammation. Here, we report that unsaturated lipid-modified polyoxovanadates (ULPOVs) can restrict weight gain of diet-induced obese mice and improve their glycemic control and obesity-associated inflammation. Oral administration of the sub-nanosized ULPOVs at a low dosage for 7 weeks reduces the body weight and almost normalizes the blood glucose levels of obese mice fed on a high-fat diet. ULPOV treatment increases the activity of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and reduces intestinal caloric intake, which may be the main reason for blood sugar and body weight control. In addition to insulin-sensitizing, PPARγ activation induced by ULPOV treatment in obese mice with atopic dermatitis (AD) promotes the type 2 T helper (TH2) cell selective responses and therapeutic effects on immune dysregulation caused by obesity. These data suggest sub-nanosized polyoxovanadate clusters as a class of potential candidates to relieve symptoms accompanied by diet-induced obesity.
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