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Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D ( n  = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was −1.02% (−1.11, −0.93) in the dorzagliatin group and −0.36% (−0.45, −0.26) in the placebo group (estimated treatment difference, −0.66%; 95% CI: −0.79, −0.53; P  < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ). The DAWN study is a phase 3 clinical trial that demonstrates effective glycemic control of dorzagliatin as an add-on therapy to metfomin in patients with type 2 diabetes.

The histone acetyltransferases CREB-binding protein (CBP) and its paralogue p300 are transcriptional coactivators which are essential for a multitude of signaling pathways and energy homeostasis. However, the role of CBP/p300 HAT domain in regulating energy balance is still unclear. Here, C57BL/6 mice fed with either normal chow diet (NCD) or high-fat diet (HFD) were administrated with A-485, a recently reported selective inhibitor of CBP/p300 HAT activity for 1 week and the metabolic change was analyzed. The white adipose tissue (WAT) weight and adipocyte size were reduced in A-485-administrated mice, with decreased expressions of lipogenic genes and transcriptional factors. In the liver of A-485-treated mice, the lipid content and lipogenic gene expressions were lowered while the binding of forkhead box O1 (FOXO1) to glucose-6-phosphatase (G6Pc) promoter was reduced, leading to decreased expression of G6Pc. In primary mouse hepatocytes, A-485 abolished cAMP-elicited mRNA expressions of key gluconeogenic enzymes and promoted FOXO1 protein degradation via increasing its ubiquitination. Thus, A-485 inhibits lipogenesis in WAT and liver as well as decreases hepatic glucose production via preventing FOXO1 acetylation, leading to its protein degradation through a proteasome-dependent pathway. The specific inhibition of CBP/p300 HAT will provide a novel therapeutic approach for metabolic diseases.

Introduction To investigate the clinical significance of obesity measurement indicators in patients with type 2 diabetes mellitus(T2DM) complicated with carotid plaque. Methods A total of 1009 subjects with T2DM were recruited in the cross-sectional study, and body measurements were collected. According to the results of carotid artery ultrasound, the study subjects were divided into T2DM without carotid plaque group (NCP: n  = 617) and with carotid plaque group (WCP: n  = 392). Results Compared with the NCP group, the waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), Chinese visceral fat index (CVAI), body roundness index (BRI), body fat index (BAI), body shape index (ABSI), and abdominal volume index (AVI) were significantly increased in the WCP group ( P < 0.05). The results of multivariate stepwise logistic regression analysis showed that BAI, CVAI and ABSI had the greatest effect on carotid plaque ( P < 0.05). After adjusting for multiple confounding factors, CVAI and ABSI remained independently associated with carotid plaques, and the combination of the three indicators exhibited superior predictive value for carotid plaques. Conclusion CVAI and ABSI are closely related to the occurrence and development of carotid plaque in subjects with T2DM, and the combined application has a good effect on predicting carotid plaque.

Protein phosphorylation and dephosphorylation are widely considered to be the key regulatory factors of cell function, and are often referred to as “molecular switches” in the regulation of cell metabolic processes. A large number of studies have shown that the phosphorylation/dephosphorylation of related signal molecules plays a key role in the regulation of liver glucose and lipid metabolism. As a new therapeutic strategy for metabolic diseases, the potential of using inhibitor-based therapies to fight diabetes has gained scientific momentum. PTG, a protein phosphatase, also known as glycogen targeting protein, is a member of the protein phosphatase 1 (PP1) family. It can play a role by catalyzing the dephosphorylation of phosphorylated protein molecules, especially regulating many aspects of glucose and lipid metabolism. In this review, we briefly summarize the role of PTG in glucose and lipid metabolism, and update its role in metabolic regulation, with special attention to glucose homeostasis and lipid metabolism.

Sleep plays a crucial biological role, and mounting evidence suggests that sleep disorders negatively impact health. In contemporary society, sleep disorders, such as sleep deprivation, insomnia, disrupted sleep-wake disorders, and circadian rhythm disorders, are widespread. Sleep disorders affect hormone production and secretion, which lead to endocrine changes, including impaired glucose tolerance, decreased insulin sensitivity, hepatic steatosis, and increased inflammatory responses, all of which accelerate the onset of various diseases. To support optimal metabolic and cardiovascular health, maintaining a consistent sleep schedule and practicing good sleep hygiene are essential.

Background Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs). We previously identified a small molecule peptide from Schistosoma japonicum and named it SJMHE1. SJMHE1 can suppress delayed-type hypersensitivity, collagen-induced arthritis and asthma in mice. In this study, we assessed the effects of SJMHE1 on dextran sulfate sodium (DSS)-induced acute and chronic colitis. Methods Acute and chronic colitis were induced in C57BL/6 mice by DSS, following which the mice were injected with an emulsifier SJMHE1 or phosphate-buffered saline. The mice were then examined for body weight loss, disease activity index, colon length, histopathological changes, cytokine expression and helper T (Th) cell subset distribution. Results SJMHE1 treatment significantly suppressed DSS-induced acute and chronic colitis, improved disease activity and pathological damage to the colon and modulated the expression of pro-inflammatory and anti-inflammatory cytokines in splenocytes and the colon. In addition, SJMHE1 treatment reduced the percentage of Th1 and Th17 cells and increased the percentage of Th2 and regulatory T (Treg) cells in the splenocytes and mesenteric lymph nodes of mice with acute colitis. Similarly, SJMHE1 treatment upregulated the expression of interleukin-10 (IL-10) mRNA, downregulated the expression of IL-17 mRNA and modulated the Th cell balance in mice with chronic colitis. Conclusions Our data show that SJMHE1 provided protection against acute and chronic colitis by restoring the immune balance. As a small molecule, SJMHE1 might be a novel agent for the treatment of IBDs without immunogenicity concerns. Graphical abstract

Hashimoto's thyroiditis (HT) represents the most common organ-specific autoimmune disease. Inflammatory factors and reactive oxygen species (ROS) play detrimental roles during the pathogenesis of HT. In this study, we found that thyroid follicular cells (TFCs) from HT patients expressed an elevated level of interleukin-23 (IL-23), which contributed to autophagy suppression and ROS accumulation. Additionally, IL-23-induced autophagy suppression and ROS accumulation in human TFCs was attributed to AKT/mTOR/NF-κB signaling pathway activation. Inhibition of either IL-23 by a specific neutralization antibody, or mTOR by rapamycin, or NF-κB by IKK-16, significantly reversed the autophagy suppression and ROS accumulation. These results demonstrate a key role for IL-23 in HT pathogenesis and provide a potential therapeutic strategy against IL-23 or its signaling pathway in HT.

Objectives Betatrophin is a widely used diagnostic marker for type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational DM (GDM) is unclear. We evaluated the relationship between betatrophin and the risk of GDM as well as the ability of betatrophin to predict postpartum type 2 DM (PDM). Methods In total, 386 patients were categorized into those with and without PDM. All underwent the oral glucose tolerance test while pregnant. Betatrophin was assessed to examine the diagnostic characteristics of GDM. Results The betatrophin concentration was remarkably higher in patients with than without GDM. The patients were categorized into three groups; those with a betatrophin concentration of 300 to 600 pg/mL and >600 pg/mL had a higher risk of GDM after adjusting for body mass index, age, homeostatic model assessment–insulin resistance (HOMA-IR) concentration, and betatrophin concentration than those with a betatrophin concentration of <300 pg/mL. The HOMA-IR concentration tended to increase as the betatrophin concentration increased, and betatrophin was independently associated with GDM after adjusting for confounders. The betatrophin concentration was higher among pregnant patients with than without PDM. Conclusions Betatrophin has high sensitivity but low specificity for diagnosing GDM and may be a promising predictor of PDM.

Adiponectin is an important adipokine exclusively secreted from adipose tissue. Growing evidence suggests that adiponectin inhibits the growth of cancer cells and reduces cancer risk. Many studies have examined the association between circulating adiponectin levels and the risk of breast cancer. However, the results of numerous epidemiological studies have been inconsistent. The aim of the present study was to conduct a systematic review and a meta-analysis on the association between circulating adiponectin levels and the risk of breast cancer. PubMed, MEDLINE, EMBASE, and ISI Web of Science were searched to identify all observational studies that examined the relationship between circulating adiponectin and breast cancer. Standard mean difference (SMD) values and 95% confidence intervals (CIs) were estimated and pooled using the meta-analysis methodology. Summary effect estimates were derived using a random effects meta-analysis model. The analysis included eight studies that met the study criteria and described the relationship between circulating adiponectin levels and breast cancer. A total of 1803 participants and 885 cases of breast cancer were included in this meta-analysis. Serum total adiponectin concentrations were lower in patients with breast cancer, with a pooled SMD of –0.39 μg/ml (95% CI –0.618 to –0.161, P = 0.001). However, adiponectin levels were not associated with the risk of breast cancer in premenopausal women [four studies, random effects SMD = 0.02 μg/ml (95% CI –0.164 to 0.204, P = 0.829)]. These results collectively suggest that lower adiponectin levels are associated with a higher risk of breast cancer in postmenopausal women.