Obesity continues to increase worldwide. The primary cause of obesity is overeating, but the development of pharmacological treatments for obesity related to overeating has taken longer than expected. Recently, agonists of glucagon-like peptide-1 (GLP-1) receptor, designed based on the gut hormone GLP-1, have been developed as anti-obesity drugs and have demonstrated remarkable efficacy in treating both obesity and diabetes. Meanwhile, recent research using factors that promote GLP-1 secretion has highlighted the significance of endogenous GLP-1 function. This review provides an overview of the anorexigenic effects, adverse effects, and their underlying mechanisms of GLP-1 receptor agonists and endogenous gut-derived GLP-1. Furthermore, it discusses the potential anti-obesity effects of dual agonists targeting both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the GLP-1 receptor, which have gained attention in recent years. Finally, we compare the beneficial effects of GLP-1 receptor agonists and meal-induced gut GLP-1 secretion on overeating-induced obesity and discuss how combining these approaches may complement each other’s limitations and serve as a promising long-term strategy for preventing and treating obesity.

Background/Objectives: Rare sugars, which naturally exist in small quantities, have gained attention as next-generation functional sugars due to their sweetness and low calorie content. Some of them have already been commercialized. Rare sugar-containing syrups, produced through alkaline isomerization of high-fructose corn syrup, are effective in preventing obesity and type 2 diabetes. However, the mechanisms underlying these effects remain incompletely understood. Recently, D-allulose has been found to improve hyperphagic obesity by stimulating the secretion of the intestinal hormone glucagon-like peptide-1 (GLP-1). The present study aimed to determine the comparative effects of aldohexoses (D-glucose, D-allose) and ketohexoses (D-fructose, D-allulose, D-tagatose, D-sorbose) on GLP-1 secretion and food intake in male mice. Method and Results: Single peroral administration of four ketohexoses at 1 and 3 g/kg, but not aldohexoses at 1 and 3 g/kg, significantly increased plasma GLP-1 concentrations with comparable efficacy. Moreover, these ketohexoses at 1 g/kg suppressed food intake in the short term, an effect blunted by GLP-1 receptor antagonism. In contrast, zero-calorie D-allose at 3 g/kg suppressed feeding without raising plasma GLP-1 levels. Conclusions: These results demonstrate that D-allulose, D-tagatose, and D-sorbose, which are low-calorie rare sugars classified as ketohexoses, suppress food intake through promoting GLP-1 secretion, showing their potential to prevent and/or ameliorate type 2 diabetes, obesity and related diseases.

Acupressure on ST36 (Zusanli), located on the lower leg, commonly used to optimize autonomic nerve activity and systemic blood flow in traditional Chinese medicine. However, its efficacy remains controversial. This study hypothesized that a single acupressure on ST36 attenuates sympathetic nerve activity and mitigate skin vasoconstriction in response to cold stimulation. Twelve participants received either 5-min acupressure or sham pressure in the right ST36; subsequently, their left hand was immersed in cold water (10°C) for 10 min. Heart rate (HR), arterial pressure, skin temperature, and blood flow in both fingers were monitored. Autonomic nerve activity was assessed by HR variability. Water immersion decreased skin temperature and blood flow in both fingers with an increase in arterial pressure. However, there were no differences in these values or HR variability between the acupressure and sham trials. Acupressure on ST36 affected neither sympathetic nerve activity nor skin vasoconstrictive response during cold-water immersion.

Food-induced anaphylaxis is a life-threatening allergic reaction in which endogenous sympathoadrenal responses play a critical role in maintaining physiological homeostasis. However, the functional status of autonomic pathways regulating adrenal catecholamine output during anaphylaxis remains unclear. Using a mouse model of food allergy-induced anaphylaxis, we examined the vagal afferent-medullary C1 neuron-adrenal sympathetic pathway and adrenal adrenergic function. Ovalbumin challenge induced hypotension, hypothermia, metabolic acidosis, and elevated plasma catecholamines. Despite severe systemic deterioration, vagal afferent stimulation and optogenetic activation of C1 neurons continued to evoke robust adrenal sympathetic responses, indicating preserved autonomic regulation. In contrast, adrenal transcriptomic analysis revealed enrichment of hypoxia-related pathways and selective suppression of phenylethanolamine N-methyltransferase (PNMT), a key enzyme for adrenaline synthesis. Oxygen supplementation partially restored PNMT expression, increased plasma adrenaline levels, and improved physiological outcomes. These findings identify hypoxia-associated adrenal dysfunction as a potential limitation of endogenous adrenergic compensation during anaphylactic shock.