Fatty acid desaturation is essential for C. elegans longevity at high temperature

•High temperature increases unsaturated fatty acids at the organismal level.•Fatty acid desaturation is required for survival at high temperature in C. elegans.•Oleic acid promotes survival at high temperature by activating defense genes.•HSF-1 links oleic acid to defense response via histone acetylation. Metabolic reprogramming is crucial for the adaptation to environmental temperature stress. It is generally accepted that fatty acid (FA) desaturation is suppressed at high temperature, which decreases the ratio of unsaturated FAs to saturated FAs (UFAs/SFAs) to maintain the fluidity of cell membranes and favor cellular survival. Here by working in C. elegans, we found that FA desaturation is essential for longevity in response to temperature upshift at the organismal level, opposite to its role in cellular survival. High temperature unexpectedly increases the contents of total fat and multiple UFA species. Specifically, monounsaturated oleic acid (OA) is required for animal survival at high temperature. Mechanistic study showed that OA acts through HSF-1, which in turn promotes histone acetylation as well as the expression of defense genes that are crucial for longevity at high temperature. Together, our findings reveal an unprecedented role for FA desaturation in organismal fitness to temperature upshift, and implicate divergent metabolic requirements between cellular and organismal survival upon temperature stress.