Obesity is a major public health concern globally. Plant-based ingredients have been proposed as alternative treatments for obesity. L-Theanine (THE), a unique nutraceutical component of tea, is known for its neuroprotective and cognitive benefits. However, there are few reports on THE’s effects and mechanisms in improving obesity and its complications. In this study, the alleviating effects and potential mechanisms of THE on obesity-related complications (ORCs) induced by a high-fat diet(HFD) in mice were explored by performing biochemical, hepatic transcriptomics, and plasma metabolomics analyses. The results indicated THE (900 mg/kg of body weight) was effective in mitigating ORCs by decreasing body weight gain and fat deposition, improving glycolipid metabolism disorders, inflammation dysregulation, and alleviating fatty liver formation due to long-term HFD. The hepatic transcriptomics data suggested that THE intervention suppresses the lipid metabolism and inflammation pathways in HFD-fed mice, thereby inhibiting hepatic steatosis and inflammation. Moreover, plasma metabolomics analysis revealed that THE exhibited positive effects on the homeostasis of plasma metabolite balance, such as phosphatidylcholine (PC(14:0/18:1)), phosphatidylethanolamine (Lyso-PE(14:0)), phosphatidic acid (PA(16:0e/18:0)), stigmasterol, and deoxycholic acid glycine conjugate. These metabolites were strongly correlated with ORC-related indicators. Our results indicated that THE, as a functional food additive, possesses potential for ORC alleviation. However, the exact molecular mechanism of how THE alleviates ORCs needs to be investigated in the future.

Background: Obesity is a chronic metabolic disease that has emerged as a major global public health concern. Obesity complications refer to a range of metabolic, neurological and behavioral disorders. Complex interaction mechanisms exist between obesity and the brain, including neuroendocrine regulation, center inflammatory responses, the gut–brain axis, and obesity-related cognitive impairment. Polyphenols are naturally occurring bioactive compounds widely found in plants. Recent research indicates that polyphenols may modulate the brain through multiple pathways, thereby ameliorating obesity complications. However, no data set available to summarize neuroregulatory effects of dietary polyphenols on obesity complication. Methods: The latest data available were collected to review research progress focusing on neuroregulatory roles of polyphenols on obesity complication. Results: This review summarizes the interaction between obesity and the brain and further explores the effects of polyphenols on obesity-related neurological disorders, with particular emphasis on their roles in appetite regulation, central neuroinflammation, brain leptin and insulin resistance, gut–brain axis modulation, and cognitive improvement. Finally, future perspectives are discussed. Conclusions: This paper may provide a new theoretical support and research direction for the potential of polyphenols against obesity-related neurological complications.