Trans, trans-2,4-decadienal, a lipid peroxidation product, aggravates insulin resistance in obese mice by promoting adipose inflammation.

Peroxidation of polyunsaturated fatty acids results in the creation of numerous α, β-unsaturated aldehydes, many of which are complicated by the development of diabetes. Trans, trans-2,4-decadienal (DDE) is a dietary α, β-unsaturated aldehyde that is commonly found in food and the environment. However, it is unknown whether DDE exposure has some negative effects on glucose homeostasis and insulin sensitivity. This study investigated the biological effects of long-term DDE exposure in normal chow diet (NCD)-fed non-obese mice and high-fat diet (HFD)-fed obese mice. Results showed that oral administration of DDE for 14 weeks did not cause severe toxicity in NCD-fed non-obese mice but had significant adverse effects in HFD-fed obese mice. It was found that DDE exposure caused significant increases in LDL and ALT levels and aggravated glucose intolerance and insulin resistance in obese mice. Moreover, DDE robustly accumulated in adipose tissue and promoted the impairment of the insulin signaling pathway in the adipose tissue of obese mice while not affecting the skeletal muscle or liver. Mechanistically, DDE aggravated adipose tissue inflammation by promoting M1 macrophage accumulation and increasing proinflammatory cytokines in the adipocytes of obese mice, thus leading to impaired systemic insulin resistance. These findings provide crucial insights into the potential health impacts of long-term DDE exposure.