The lymphatic vasculature plays important roles in the physiology of the organs in which it resides, though a clear mechanistic understanding of how this cross-talk is mediated is lacking. Single cell transcriptional profiling of human and murine adipose tissue identified the highly specific expression of neurotensin (NTS/Nts) in lymphatic endothelial cells. Nts expression is reduced by cold and by norepinephrine in an -adrenergic-dependent manner, suggesting a role in adipose thermogenesis. NTS added to brown adipose tissue explants reduced expression of thermogenic genes, and adenoviral-mediated overexpression and knock-down of NTS in vivo reduced and enhanced cold tolerance, respectively. This effect was determined to be mediated by NTSR2, which represses energy expenditure, thermogenic gene expression, and cold tolerance. Inhibition of NTSR2 improves all of these parameters and promotes energy expenditure and weight loss in obese mice. These data establish a link between adipose tissue lymphatics and adipocytes with potential therapeutic applications.