Lactate Fluxes and Plasticity of Adipose Tissues: A Redox Perspective

Abstract

Lactate, a metabolite produced when the glycolytic flux exceeds mitochondrial oxidative capacities, is now viewed as a critical regulator of metabolism by acting as both a carbon and electron carrier and a signaling molecule between cells and tissues. In recent years, increasing evidence report its key role in white, beige, and brown adipose tissue biology, and highlights new mechanisms by which lactate participates in the maintenance of whole-body energy homeostasis. Lactate displays a wide range of biological effects in adipose cells not only through its binding to the membrane receptor but also through its transport and the subsequent effect on intracellular metabolism notably on redox balance. This study explores how lactate regulates adipocyte metabolism and plasticity by balancing intracellular redox state and by regulating specific signaling pathways. We also emphasized the contribution of adipose tissues to the regulation of systemic lactate metabolism, their roles in redox homeostasis, and related putative physiopathological repercussions associated with their decline in metabolic diseases and aging.

Brown Adipose Tissue—A Translational Perspective

“…Lactate is the most abundant product from the very high glucose metabolic rate of brown adipocytes ( 83 , 84 ) and can exert local effects through membrane receptor–mediated mechanisms and changes in cellular redox state (see [ 295 ] for review). Lactate is known to inhibit intracellular adipocyte TG lipolysis through the activation of GPR81-mediated reduction in adenylate cyclase ( 296 , 297 ).…”

Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial

“…Indeed, there is a role of adipose tissue, besides skeletal muscle, for glucose uptake and lactate metabolism. 30 However, in situ measurements of lactate in adipose tissue showed no difference in results between the two study arms. Unfortunately, we had no measurements of adipose tissue blood flow, preventing proper evaluation of subcutaneous lactate and glycerol release.…”

Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a mouse model of Friedreich’s ataxia

“…The switch towards glycolytic metabolism may originate from defective mitochondrial respiration and/or scarce oxygen availability due to reduced angiogenesis and vascularization. Lactate is a redox molecule that, in adipose tissues, displays a wide range of biological effects both through its binding to membrane receptors and its transport and subsequent effect on intracellular metabolism (Lagarde et al, 2021). Lactate produced by adipocytes inhibits lipolysis in an autocrine/paracrine manner through inhibition of PKA (Ahmed et al, 2010).…”