Tisochrysis lutea F&M-M36 Mitigates Risk Factors of Metabolic Syndrome and Promotes Visceral Fat Browning through β3-Adrenergic Receptor/UCP1 Signaling.

Pre-metabolic syndrome (pre-MetS) may represent the best transition phase to start treatments aimed at reducing cardiometabolic risk factors of MetS. In this study, we investigated the effects of the marine microalga Tisochrysis lutea F&M-M36 ( T. lutea ) on cardiometabolic components of pre-MetS and its underlying mechanisms. Rats were fed a standard (5% fat) or a high-fat diet (20% fat) supplemented or not with 5% of T. lutea or fenofibrate (100 mg/Kg) for 3 months. Like fenofibrate, T. lutea decreased blood triglycerides ( p < 0.01) and glucose levels ( p < 0.01), increased fecal lipid excretion ( p < 0.05) and adiponectin ( p < 0.001) without affecting weight gain. Unlike fenofibrate, T. lutea did not increase liver weight and steatosis, reduced renal fat ( p < 0.05), diastolic ( p < 0.05) and mean arterial pressure ( p < 0.05). In visceral adipose tissue (VAT), T. lutea , but not fenofibrate, increased the β3-adrenergic receptor (β3ADR) ( p < 0.05) and Uncoupling protein 1 (UCP-1) ( p < 0.001) while both induced glucagon-like peptide-1 receptor (GLP1R) protein expression ( p < 0.001) and decreased interleukin (IL)-6 and IL-1β gene expression ( p < 0.05). Pathway analysis on VAT whole-gene expression profiles showed that T. lutea up-regulated energy-metabolism-related genes and down-regulated inflammatory and autophagy pathways. The multitarget activity of T. lutea suggests that this microalga could be useful in mitigating risk factors of MetS.