Trehalose induces SQSTM1/p62 expression and enhances lysosomal activity and antioxidative capacity in adipocytes.

Adipocytes, which comprise the majority of white adipose tissue (WAT), are involved in obesity-related pathology via various mechanisms, including disturbed lysosomal enzymatic activity and accumulation of oxidative stress. Sequestosome 1 (SQSTM1/p62) is an autophagy marker that participates in antioxidative responses via the activation of nuclear factor erythroid-derived 2-like 2 (NRF2). Trehalose is a non-reducing disaccharide reported to suppress adipocyte hypertrophy in obese mice and improve glucose tolerance in humans.

Taurine is an amino acid with the ability to activate autophagy in adipocytes.

Alterations in adipocyte characteristics are highly implicated in the pathology of obesity. In a recent article, we demonstrated that high-fat diet-induced obesity impairs lysosomal function, thereby suppressing autophagy in mice white adipose tissue. Taurine, an amino acid naturally contained in the normal diet and existing ubiquitously in tissues, has been reported to improve insulin resistance and chronic inflammation in animal models, but underlying mechanisms remain unclear.

Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways.

Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. In addition, trehalose functions as an antioxidant though its underlying molecular mechanisms remain unclear.

Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice.

Whether obesity accelerates or suppresses autophagy in adipose tissue is still debatable. To clarify dysregulation of autophagy and its role in pathologies of obese adipose tissue, we focused on lysosomal function, protease maturation and activity, both in vivo and in vitro. First, we showed that autophagosome formation was accelerated, but autophagic clearance was impaired in obese adipose tissue.