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These authors contributed equally: Sihan Lv, Tingting Hu.

The imbalance between energy intake and energy expenditure leads to the prevalence of obesity world-widely. Strategy to simultaneously limit energy intake and promote energy expenditure will serve as a powerful mean for new obesity treatment. Here, we identified Rhamnose as a non-nutritive sweetener to promote adipose thermogenesis and energy expenditure. Rhamnose promotes cAMP production and PKA activation through dopamine receptor D1 in adipose tissue. As a result, Rhamnose administration promotes UCP1-dependent thermogenesis and ameliorates obesity in mice. Thus, we have demonstrated a Rhamnose-dopamine receptor D1-PKA axis critical for thermogenesis and Rhamnose may serve as a new therapeutic molecular diet against obesity.

This article contains supplementary material online at https://doi.org/10.2337/figshare.21667799.

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