Central Administration of Sargahydroquinoic Acid Elevates Peripheral Thermogenic Signaling and Ameliorates High Fat Diet-Induced Obesity

Abstract Sargassum serratifolium (C.Agardh) C.Agardh, a marine brown alga, has been consumed as food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome. Sargahydroquinoic acid (SHQA) is a major component in MES. However, it is unclear whether SHQA can regulate energy homeostasis through the central nervous system. To figure it out, SHQA was administrated through the third ventricle of the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Bath application of SHQA increases the intrinsic neuronal excitability of hypothalamic ARC neurons in acutely prepared brain slices. Thus, we further tested its effect on energy balance. Chronic administration of SHQA into the brain reduced bodyweight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicate that SHQA elevates thermogenic signaling pathways evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. As partial mechanisms, SHQA significantly elevated mRNA levels of genes associated with sympathetic outflow and GABA signaling pathways. Our data indicate that hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.