Notaro Nicole M, Dyck David J
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Metabol Open. 2024 Feb 28;21:100279. doi: 10.1016/j.metop.2024.100279. eCollection 2024 Mar.
Ghrelin increases in the circulation prior to entrained mealtimes, with the acylated (AG) form functioning to stimulate food intake and growth hormone release. Acutely, AG induces whole-body insulin resistance, potentially to maintain glycemia between meals. Alternatively, chronic administration of both AG and the unacylated isoform of ghrelin (unAG) is associated with improved skeletal muscle insulin sensitivity as well as reduced intramuscular lipids and inflammation. This may be due to effects on lipid metabolism, with ghrelin promoting storage of fat in adipose and liver while stimulating oxidation in skeletal muscle, preventing ectopic lipid accumulation. This is of specific relevance in the handling of meal-derived lipids, as ghrelin rises preprandially with effects persisting for 2-3 h following exposure in skeletal muscle, coinciding with elevated plasma FFAs. We hypothesize that ghrelin acts as a preparatory signal for incoming lipids, as well as a regulatory hormone for their use and storage. The effects of ghrelin on skeletal muscle are lost with high fat diet feeding and physical inactivity, potentially being implicated in the pathogenesis of metabolic disease. This review summarizes the metabolic effects of both ghrelin isoforms on peripheral tissues including the pancreas, adipose, liver, and skeletal muscle. Additionally, we speculate on the physiological relevance of these effects in vivo and suggest that ghrelin may be a key regulatory hormone for nutrient handling in the postprandial state.
在规律进餐时间之前，胃饥饿素在循环中的水平会升高，其酰化形式（AG）可刺激食物摄入和生长激素释放。急性情况下，AG会诱发全身胰岛素抵抗，这可能是为了在两餐之间维持血糖水平。另外，长期给予AG和胃饥饿素的非酰化异构体（unAG）可改善骨骼肌胰岛素敏感性，并减少肌肉内脂质和炎症。这可能是由于对脂质代谢的影响，胃饥饿素促进脂肪在脂肪组织和肝脏中的储存，同时刺激骨骼肌中的氧化，防止异位脂质积累。这在处理餐源性脂质方面具有特殊意义，因为胃饥饿素在餐前升高，其作用在骨骼肌暴露后持续2 - 3小时，与血浆游离脂肪酸升高同时发生。我们推测胃饥饿素作为摄入脂质的预备信号，以及其使用和储存的调节激素。高脂肪饮食喂养和缺乏身体活动会使胃饥饿素对骨骼肌的作用丧失，这可能与代谢疾病的发病机制有关。本综述总结了两种胃饥饿素异构体对包括胰腺、脂肪组织、肝脏和骨骼肌在内的外周组织的代谢影响。此外，我们推测了这些作用在体内的生理相关性，并表明胃饥饿素可能是餐后状态下营养物质处理的关键调节激素。
