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Scope: Diet and exercise are significant players in obesity and metabolic diseases. Time-restricted feeding (tRF) has been shown to improve metabolic responses by regulating circadian clocks but whether it acts synergically with exercise remains unknown. It is hypothesized that forced exercise alone or combined with tRF alleviates obesity and its metabolic complications., Methods and Results: Male C57bl6 mice are fed with high-fat or a control diet for 12 weeks either ad libitum or tRF for 10 h during their active period. High-fat diet (HFD)-fed mice are divided into exercise (treadmill for 1 h at 12 m min -1 alternate days for 9 weeks and 16 m min -1 daily for the following 3 weeks) and non-exercise groups. tRF and tRF-Ex significantly decreased body weight, food intake, and plasma lipids, and improved glucose tolerance. However, exercise reduced only body weight and plasma lipids. tRF and tRF-Ex significantly downregulated Fasn, Hmgcr, and Srebp1c, while exercise only Hmgcr. HFD feeding disrupted clock genes, but exercise, tRF, and tRF-Ex coordinated the circadian clock genes Bmal1, Per2, and Rev-Erbα in the liver, adipose tissue, and skeletal muscles., Conclusion: HFD feeding disrupted clock genes in the peripheral organs while exercise, tRF, and their combination restored clock genes and improved metabolic consequences induced by high-fat diet feeding., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Obesity is one of the major global threats to human health and risk factors for cardiometabolic diseases and certain cancers. Glucagon-like peptide-1 (GLP-1) plays a major role in appetite and glucose homeostasis and recently the USFDA approved GLP-1 agonists for the treatment of obesity and type 2 diabetes. GLP-1 is secreted from enteroendocrine L-cells in the distal part of the gastrointestinal (GI) tract in response to nutrient ingestion. Endogenously released GLP-1 has a very short half-life of <2 min and most of the nutrients are absorbed before reaching the distal GI tract and colon, which hinders the use of nutritional compounds for appetite regulation. The review article focuses on nutrients that endogenously stimulate GLP-1 and peptide YY (PYY) secretion via their receptors in order to decrease appetite as preventive action. In addition, various delivery technologies such as pH-sensitive, mucoadhesive, time-dependent, and enzyme-sensitive systems for colonic targeting of nutrients delivery are described. Sustained colonic delivery of nutritional compounds could be one of the most promising approaches to prevent obesity and associated metabolic diseases by, e.g., sustained GLP-1 release., (© 2022 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)