Numerous studies have found that inflammation in adipose tissue is the major source of obesity-induced systemic insulin resistance. Obesity-related changes in circulating LPS levels, as well as hypoxia/HIF-1α activation, have been proposed to enhance obesity-induced inflammation. However, little was known about what causes obesity-induced inflammation. Researchers identified lactate as a critical mediator of obesity-induced inflammation and systemic insulin resistance in the investigation. Specific deletion of Slc16a1, which encodes MCT1, the principal lactate transporter in adipose tissues, significantly raises blood levels of proinflammatory cytokines and worsens systemic insulin resistance without affecting adiposity. In addition, the deletion of Slc16a1 in adipocytes increases intracellular lactate while decreasing circulatory lactate concentration.

Lactate retention caused by Slc16a1 deletion causes adipocyte death and cytokine release. Locally recruited macrophages exacerbate the inflammation by releasing proinflammatory cytokines into the bloodstream, resulting in insulin resistance in peripheral organs. The work suggested that lactate within adipocytes has a vital biological function in the relationship between obesity and insulin resistance and that harnessing lactate in adipocytes might be a potential way to break this link.

Reference:diabetesjournals.org/diabetes/article-abstract/71/4/637/139309/Lactate-Is-a-Key-Mediator-That-Links-Obesity-to?redirectedFrom=fulltext