1.The regulation and mechanism of apolipoprotein A5 on myocardial lipid deposition.
Xiao-Jie YANG ; Jiang LI ; Jing-Yuan CHEN ; Teng-Teng ZHU ; Yu-Si CHEN ; Hai-Hua QIU ; Wen-Jie CHEN ; Xiao-Qin LUO ; Jun LUO
Acta Physiologica Sinica 2025;77(1):35-46
The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals
;
Humans
;
Mice
;
Myocytes, Cardiac/metabolism*
;
Obesity/physiopathology*
;
Male
;
Apolipoprotein A-V/blood*
;
Lipid Metabolism/physiology*
;
Milk Proteins/blood*
;
Myocardium/metabolism*
;
Diet, High-Fat
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Antigens, Surface/physiology*
;
Mice, Inbred C57BL
;
Cells, Cultured
;
Female
2.Local overexpression of miR-429 sponge in subcutaneous white adipose tissue improves obesity and related metabolic disorders.
Liu YAO ; Wen-Jing XIU ; Chen-Ji YE ; Xin-Yu JIA ; Wen-Hui DONG ; Chun-Jiong WANG
Acta Physiologica Sinica 2025;77(3):441-448
Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals
;
MicroRNAs/physiology*
;
Obesity/metabolism*
;
Mice
;
Adipose Tissue, White/metabolism*
;
Metabolic Diseases
;
Subcutaneous Fat/metabolism*
;
Male
;
Uncoupling Protein 1/metabolism*
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Diet, High-Fat
;
Mice, Inbred C57BL
3.Advances in the function and mechanisms of stearoyl-CoA desaturase 1 in metabolic diseases.
Qin SUN ; Xiao-Rui XING ; Cheng LIU ; Dan-Dan JIA ; Ru WANG
Acta Physiologica Sinica 2025;77(3):545-562
Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism*
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Humans
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Metabolic Diseases/physiopathology*
;
Lipid Metabolism/physiology*
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Animals
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Obesity/enzymology*
;
Non-alcoholic Fatty Liver Disease
4.Research progress on the comorbidity mechanism of sarcopenia and obesity in the aging population.
Hao-Dong TIAN ; Yu-Kun LU ; Li HUANG ; Hao-Wei LIU ; Hang-Lin YU ; Jin-Long WU ; Han-Sen LI ; Li PENG
Acta Physiologica Sinica 2025;77(5):905-924
The increasing prevalence of aging has led to a rising incidence of comorbidity of sarcopenia and obesity, posing significant burdens on socioeconomic and public health. Current research has systematically explored the pathogenesis of each condition; however, the mechanisms underlying their comorbidity remain unclear. This study reviews the current literature on sarcopenia and obesity in the aging population, focusing on their shared biological mechanisms, which include loss of autophagy, abnormal macrophage function, mitochondrial dysfunction, and reduced sex hormone secretion. It also identifies metabolic mechanisms such as insulin resistance, vitamin D metabolism abnormalities, dysregulation of iron metabolism, decreased levels of nicotinamide adenine dinucleotide, and gut microbiota imbalances. Additionally, this study also explores the important role of genetic factors, such as alleles and microRNAs, in the co-occurrence of sarcopenia and obesity. A better understanding of these mechanisms is vital for developing clinical interventions and preventive strategies.
Humans
;
Sarcopenia/physiopathology*
;
Obesity/physiopathology*
;
Aging/physiology*
;
Autophagy/physiology*
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Insulin Resistance
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Comorbidity
;
Vitamin D/metabolism*
;
Gonadal Steroid Hormones/metabolism*
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Gastrointestinal Microbiome
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Mitochondria
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MicroRNAs
5.The role of selenoproteins in adipose tissue and obesity.
Yun-Fei ZHAO ; Yu-Hang SUN ; Tai-Hua JIN ; Yue LIU ; Yang-Di CHEN ; Wan XU ; Qian GAO
Acta Physiologica Sinica 2025;77(5):939-955
Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism*
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Adipose Tissue/physiology*
;
Obesity/metabolism*
;
Humans
;
Animals
;
Selenium
7.Network pharmacology, molecular docking, and animal experiments reveal mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children.
Yong-Kai YIN ; Chang-Miao NIU ; Li-Ting LIANG ; Mo DAN ; Tian-Qi GAO ; Yan-Hong QIN ; Xiao-Ning YAN
China Journal of Chinese Materia Medica 2025;50(1):228-238
Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals
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Drugs, Chinese Herbal/pharmacology*
;
Molecular Docking Simulation
;
Adipose Tissue/immunology*
;
Mice
;
Male
;
Humans
;
Network Pharmacology
;
Macrophages/immunology*
;
Mice, Inbred C57BL
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Child
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Protein Interaction Maps/drug effects*
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Obesity/genetics*
;
Inflammation/drug therapy*
8.Construction of core outcome set for clinical research on traditional Chinese medicine treatment of simple obesity.
Tong-Tong WU ; Yan YU ; Qian HUANG ; Xue-Yin CHEN ; Fu-Ming-Xiang LIU ; Li-Hong YANG ; Chang-Cai XIE ; Shao-Nan LIU ; Yu CHEN ; Xin-Feng GUO
China Journal of Chinese Materia Medica 2025;50(12):3423-3430
Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans
;
Obesity/therapy*
;
Medicine, Chinese Traditional
;
Randomized Controlled Trials as Topic
;
Treatment Outcome
;
Drugs, Chinese Herbal/therapeutic use*
9.Obesogenic characteristics of primary schools in an urban Philippine municipality: A descriptive study
Christian Joshua V. Cacatian ; Julia Czen N. Melendres ; Nisha Joelle F. Caguntas ; Jasmine C. Manalang ; Nicole Evangeline M. Sotto ; Peter James B. Abad
Acta Medica Philippina 2025;59(Early Access 2025):1-12
BACKGROUND
With childhood overweight and obesity becoming widespread in the Philippines, there is an increased risk of developing non-communicable diseases at a younger age. The school environment, found to be associated with body mass index, offers an avenue to address and prevent school-aged obesity. However, the lack of data on the current school environment poses a barrier to improving these conditions.
OBJECTIVEThis study aimed to describe the physical, political, and sociocultural environment characteristics of primary schools in the Municipality of Pateros (Philippines) that affect nutrition and physical activity of school-aged children.
METHODSSelf-administered questionnaires for key school personnel and observational checklists were used to examine available resources, policies, and current practices for obesity prevention in five public schools in a municipality. The role perceptions of all school personnel on childhood obesity prevention were also gathered. Descriptive statistics was used to describe the number and categories of food items, functional spaces and equipment for physical activity, policies and scores of attitude toward obesity prevention. Data were collected in May to June 2019 and were analyzed descriptively.
RESULTSMajority of the schools serve food items that contain high amounts of saturated fat, sugar, or salt, provide excess calories, and are not recommended to be sold at school canteens based on guidelines by the Department of Education. While all schools have areas and functional equipment for physical activity, students have limited access to these. Policies and guidelines for nutrition were present but sparse for physical activity and obesity prevention. Positive attitude towards childhood obesity prevention was seen across all school personnel respondents.
CONCLUSIONParticipant primary schools are eager to address childhood obesity, however, the physical, political, and sociocultural environments do not seem to enable this. This situation may promote, rather than prevent, overweight and obesity among school children. This points to the need of reorientation and implementation of policies on obesity prevention to the schools as well as developing the skills of both teaching and non-teaching personnel in healthy eating and physical activity to students. School-based healthcare workers like school nurses and doctors would have critical roles in supporting schools in this regard.
Human ; Obesity ; Schools ; Primary Schools ; Noncommunicable Diseases
10.Micronutrient intake and diet quality of overweight/obese Filipino adults in the National Capital Region, Philippines
Jade Q. Florento ; Kim Leonard G. Dela luna ; Charina A. Javier ; Eldridge B. Ferrer
Acta Medica Philippina 2025;59(10):85-94
OBJECTIVES
This study aims to describe the micronutrient intake and diet quality of overweight and obese Filipino adults in the National Capital Region (NCR). Specifically, it seeks to assess micronutrient inadequacy among these individuals and analyze differences in food intake based on their sociodemographic profiles and lifestyle habits.
METHODSThis analytical cross-sectional study utilized data from the Expanded National Nutrition Survey (ENNS) conducted in 2018, 2019, and 2021 by the Department of Science and Technology-Food and Nutrition Research Institute (DOST-FNRI). A total of 3,154 overweight and obese subjects were included. ANOVA and Kruskal-Wallis tests were employed to analyze the food groups consumed by these adults.
RESULTSMajority of overweight and obese adults were found to be inadequate in vitamin A (81.7%), vitamin C (88.4%), thiamin (62.5%), riboflavin (70.7%), iron (69.8%), and calcium (88.7%). Significant differences were observed in the mean intake of various food groups across different age groups, sexes, civil statuses, wealth quintiles, educational attainments, employment statuses, and smoking and drinking statuses.
CONCLUSIONFilipino adults who are overweight and obese, and residing in urban settings face significant challenges related to micronutrient inadequacy. When their food intake was assessed based on sociodemographic and lifestyle characteristics, it was found that their diets were more calorie-dense than nutrient-dense. To address this issue, it is recommended to encourage a wider variety of nutrient-dense foods among overweight and obese adults.
Food Intake ; Eating ; Micronutrients ; Overweight ; Obesity ; Nutritional Status


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