Diabetes & Metabolism Journal最新文献

{"title":"Effect of 4 Weeks Resonance Frequency Breathing on Glucose Metabolism and Autonomic Tone in Healthy Adults.","authors":"Benedict Herhaus, Andreas Peter, Julia Hummel, Thomas Kubiak, Martin Heni, Katja Petrowski","doi":"10.4093/dmj.2024.0647","DOIUrl":"https://doi.org/10.4093/dmj.2024.0647","url":null,"abstract":"<p><strong>Background: </strong>The autonomic nervous system plays a crucial role in the brain's communication with metabolically important peripheral organs, modulating insulin sensitivity and secretion. Increased sympathetic tone is a common feature in prediabetes and diabetes. The parasympathetic nervous system activity might be improvable through resonance frequency breathing (RFB) with heart rate variability biofeedback (HRV-BF) training.</p><p><strong>Methods: </strong>We here investigated the effect of a 4-week mobile RFB-HRV-BF intervention on glucose metabolism and HRV of 30 healthy adults (17 females; mean age 25.77±3.64 years; mean body mass index 22.65±2.95 kg/m2). Before and after the intervention, glucose metabolism was assessed by 75 g oral glucose tolerance tests (with blood sampling every 30 minutes over 2 hours) and HRV was measured through electrocardiography.</p><p><strong>Results: </strong>RFB-HRV-BF training did not influence glucose metabolism in healthy adults but reduced fasting as well as 2-hour-postload glucose in participants categorized as more insulin resistant before the intervention. In addition, RFB-HRV-BF training was associated with an increase in the time and frequency domain HRV parameters standard deviation of all NN-intervals, root mean square successive differences, HRV high-frequency and HRV low-frequency after 4 weeks of intervention.</p><p><strong>Conclusion: </strong>Our findings introduce RFB-HRV-BF training as an effective tool to modulate the autonomic nervous system with a shift towards the parasympathetic tone. Along with the observed decrease in glycemia in those with lower insulin sensitivity, RFB-HRV-BF training emerges as a promising non-pharmacological approach to improve glucose metabolism which has to be further investigated in prediabetes and diabetes.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Milieu by Crosstalk between Glomerulus and Proximal Tubular Cells in Type 2 Diabetes Mellitus Kidney Disease.","authors":"Peong Gang Park, Juhyeon Hwang, Yongjun Kim, Minki Hong, Donghwan Yun, Haein Yoon, Chaelin Kang, Sohyun Bae, Soo Heon Kwak, Yong Chul Kim, Kyung Chul Moon, Dong-Sup Lee, Yon Su Kim, Hee Gyung Kang, Hyun Je Kim, Seung Seok Han","doi":"10.4093/dmj.2024.0535","DOIUrl":"https://doi.org/10.4093/dmj.2024.0535","url":null,"abstract":"<p><strong>Background: </strong>Due to the limited availability of therapeutic agents for type 2 diabetic kidney disease (T2DKD), there is a need for further knowledge derived from experimental models and innovative techniques. In addressing this issue, single-cell RNA sequencing (scRNA-seq) has been exclusively applied to a genetically modified diabetic kidney disease model, but not to an induced model representing T2DKD. Herein, we analyzed scRNA-seq and other experiments from an induced T2DKD model and validated the results in human-derived biospecimens.</p><p><strong>Methods: </strong>The model was induced by combining a high-fat diet with streptozotocin to simulate induced T2DKD. scRNA-seq, histological, and flow cytometric analyses were conducted, and the results were compared with control mice. The findings were then applied to human T2DKD kidneys.</p><p><strong>Results: </strong>Biochemical and histological analyses unveiled early-stage T2DKD features, such as hyperfiltration, increased proteinuria, glomerulomegaly, and interstitial fibrosis. scRNA-seq identified that proximal tubules secreted a variety of chemokines, potentially in response to crosstalk with glomeruli. Notably, C-X-C motif chemokine 12 (CXCL12) emerged as a key player in potentially promoting T-cell recruitment. Flow cytometry substantiated T-cell infiltration into the kidney of the T2DKD model. This finding was further corroborated in human biopsied kidney tissues, showing a correlation between elevated CXCL12 levels and T2DKD progression.</p><p><strong>Conclusion: </strong>The induced T2DKD model highlights the pivotal role of CXCL12-mediated T-cell infiltration, stemming from the crosstalk between proximal tubules and glomeruli. This data serves as a foundation for future studies, promising a therapeutic target for T2DKD.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Causal Relationship and Association between Biomarkers, Dietary Intake, and Diabetic Retinopathy: Insights from Mendelian Randomization and Cross-Sectional Study.","authors":"Xuehao Cui, Dejia Wen, Jishan Xiao, Xiaorong Li","doi":"10.4093/dmj.2024.0731","DOIUrl":"https://doi.org/10.4093/dmj.2024.0731","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is a major cause of vision loss, linked to hyperglycemia, oxidative stress, and inflammation. Despite advancements in DR treatments, approximately 40% of patients do not respond effectively, underscoring the need for novel, noninvasive biomarkers to predict DR risk and progression. This study investigates causal relationships between specific biomarkers, dietary factors, and DR development using Mendelian randomization (MR) and cross-sectional data.</p><p><strong>Methods: </strong>We conducted a two-phase analysis combining MR and cross-sectional methods. First, MR analysis examined causal associations between 35 biomarkers, 226 dietary factors, and DR progression using data from the UK Biobank and Genome-Wide Association Study (GWAS) datasets. Second, a cross-sectional study with National Health and Nutrition Examination Survey (NHANES) and a clinical cohort from Tianjin Medical University Eye Hospital validated findings and explored biomarkers' predictive capabilities through a nomogram-based prediction model.</p><p><strong>Results: </strong>MR analysis identified eight biomarkers (e.g., glycosylated hemoglobin [HbA1c], high-density lipoprotein cholesterol [HDL-C]) with significant causal links to DR. Inflammatory markers and metabolic factors, such as high glucose and HDL-C levels, were strongly associated with DR risk and progression. Specific dietary factors, like cheese intake, exhibited protective roles, while alcohol intake increased DR risk. Validation within NHANES and Tianjin cohorts supported these causal associations.</p><p><strong>Conclusion: </strong>This study elucidates causal relationships between biomarkers, dietary habits, and DR progression, emphasizing the potential for personalized dietary interventions to prevent or manage DR. Findings support the use of HDL-C, HbA1c, and dietary factors as biomarkers or therapeutics in DR, though further studies are needed for broader applicability.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregravid Weight Gain Is Associated with an Increased Risk of Gestational Diabetes.","authors":"Sunmie Kim, Kyungdo Han, Su-Yeon Choi, Min Joo Kim, Sun Young Yang, Seung Ho Choi, Jeong Yoon Yim, Jin Ju Kim, Min-Jeong Kim","doi":"10.4093/dmj.2024.0491","DOIUrl":"https://doi.org/10.4093/dmj.2024.0491","url":null,"abstract":"<p><strong>Background: </strong>Studies have reported a significant association between pregravid weight gain and the subsequent development of gestational diabetes mellitus (GDM) in various populations. The current study aims to investigate this relationship using data from the Korean National Health Insurance Service database.</p><p><strong>Methods: </strong>We conducted a retrospective nationwide population-based cohort study, involving 159,798 women who gave birth between 2015 and 2017 and had undergone two national health screening examinations: 1 year (index checkup) and 3 years before (baseline checkup) their respective estimated conception date. Participants were categorized into five groups based on the extent of weight change between the two examinations: more than 10%, 5% to 10%, -5% to 5% (reference group), -10% to -5%, and more than -10%. The study assessed the association between pregravid weight change and GDM risk.</p><p><strong>Results: </strong>Among the 146,363 women analyzed, 11,012 (7.52%) were diagnosed with GDM. Multiple regression analysis revealed that women who gained 5% to 10% of their weight had a 12% increased risk of GDM (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.06 to 1.17), while those who gained ≥10% had a 34% higher risk (aOR, 1.34; 95% CI, 1.26 to 1.43). Notably, pregravid weight gain was particularly associated with GDM risk in non-obese or non-metabolic syndrome groups at index checkup.</p><p><strong>Conclusion: </strong>Pregravid weight gain showed a dose-dependent association with a higher risk of GDM. This association was more pronounced in non-obese individuals emphasizing the importance of minimizing pregravid weight gain for GDM prevention, even in non-obese women.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Healthy Lifestyle Factors and Metabolic Syndrome Risk: A Prospective Analysis of the Korean Genome and Epidemiology Study.","authors":"Jialei Fu, Sangah Shin","doi":"10.4093/dmj.2024.0427","DOIUrl":"https://doi.org/10.4093/dmj.2024.0427","url":null,"abstract":"<p><strong>Background: </strong>To investigate the association of adherence to five modifiable lifestyle factors (limiting alcohol, physical activity, limiting smoking, favorable diet quality, and adequate sleep) with metabolic syndrome (MetS) risk in Korean adults.</p><p><strong>Methods: </strong>Health Examinees Study data were used, and 41,368 participants aged 40 to 69 years were included. Cox proportional hazards regression analyses assessed the associations of individual and combined healthy lifestyle factors (32 and 16 lifestyle profiles in men and women.</p><p><strong>Results: </strong>During a median 4.2-year follow-up, 6,213 participants were newly diagnosed with MetS. Adherence to more healthy lifestyle factors (4-5 vs. 0-1) could lower MetS risk by 28% and 12% in men and women (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63 to 0.83 in men; HR, 0.88; 95% CI, 0.78 to 0.99 in women). Each additional healthy lifestyle could reduce the risk of MetS by 10% and 6% in men and women. The pooled analysis yielded similar results based on similar numbers of healthy lifestyle factors, the risk of MetS decreased as the number of healthy lifestyle factors increased.</p><p><strong>Conclusion: </strong>Adherence to more healthy lifestyle factors was inversely associated with MetS risk. These findings highlight the importance of limiting drinking in managing MetS. Future research should consider the synergistic effects of emerging lifestyle factors, such as sleep duration, on chronic disease development, while focusing on the effects of traditional lifestyle factors.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factor 21 Levels Are Associated With Perception and Neural Responses to Sweetness in Type 2 Diabetes Mellitus","authors":"Piao Kang, Ying Zhang, Dian Zeng, Dan Liu, Rui Han, Yuwei Lu, Di Cheng, Qinyi Wang, Silin Liu, Liang Wu, Qian Wu, Shujie Yu, Anran Chen, Jingyi Guo, Wenli Ge, Jiacheng Ni, Jingyi Yang, Xiaomeng Wu, Lifei Ma, Weiping Jia, Qichen Fang, Yuehua Li, Huating Li","doi":"10.4093/dmj.2024.0390","DOIUrl":"https://doi.org/10.4093/dmj.2024.0390","url":null,"abstract":"<p><strong>Background: </strong>The relationship between fibroblast growth factor 21 (FGF21) and sweet taste perception and preference in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to investigate this relationship and examine the neural responses of T2DM patients to high-calorie sweet (HCS) food pictures, further exploring its correlation with FGF21 levels.</p><p><strong>Methods: </strong>We assessed sweet taste perception and preference in 40 T2DM patients and 41 controls using classical scales. Subsequently, the neural responses of 11 T2DM patients and 11 controls to HCS pictures were examined using functional magnetic resonance imaging. FGF21 levels were measured using chemiluminescent immunoassay, and the correlations with taste perception and neural responses were analyzed.</p><p><strong>Results: </strong>Increased FGF21 levels were associated with decreased sweet perception and increased sweet taste preference in T2DM patients. Compared to control, T2DM patients exhibited greater neural activations in the orbitofrontal cortex, anterior cingulate cortex (ACC), thalamus, and hippocampus (HCS vs. non-food) as well as the putamen (HCS vs. low-calorie food). Notable differences were observed in the parahippocampal gyrus, insula, ACC, and hippocampus in T2DM patients (HCS vs. high-calorie non-sweet). Additionally, FGF21 accounted for 30.39% and 32.4% of the associations between T2DM and ACC, and parahippocampal gyrus, respectively.</p><p><strong>Conclusion: </strong>FGF21 levels were independently associated with changes in sweet taste perception and preference in T2DM patients and were significantly associated with activation in reward-related brain regions. This study reveals the potential role of FGF21 in regulating responses to sweet foods in T2DM and provides insight to develop new therapeutic strategies for diabetes.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Enrollment in Diabetes Pay-for-Performance Program Reduced Loss of Life Expectancy in Newly-Diagnosed Patients with Type 2 Diabetes Mellitus.","authors":"Yu-Ching Chen, Wei-Ming Wang, Boniface J Lin, Jung-Der Wang, Li-Jung Elizabeth Ku","doi":"10.4093/dmj.2024.0507","DOIUrl":"https://doi.org/10.4093/dmj.2024.0507","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is associated with reduced lifespan. To explore pay-for-performance (P4P) program and life expectancy (LE), we investigated the impact of interval between diabetes diagnosis and enrollment in P4P program on loss-of-LE among patients with diabetes in Taiwan.</p><p><strong>Methods: </strong>From diabetes mellitus health database, which collected all newly-diagnosed patients with diabetes by calendar year, we selected patients, aged 40 to 64, with 503,662 in P4P group and 450,071 in non-P4P group, respectively, from 2004 to 2015, and followed them until the end of 2018 using Kaplan-Meier survival analysis. We simulated age-, gender-, and calendar yearmatched referents for each group through Monte Carlo method from Taiwan's vital statistics. We constructed a restricted cubic spline model on logit-transformed relative survival between each group and its corresponding matched referents, and applied a rolling-over algorithm month-by-month to extrapolate the survival function of each index group to lifetime to estimate the LE, which was subtracted from that of matched referents to obtain the loss-of-LE.</p><p><strong>Results: </strong>We found stratified analysis by interval showed that the earlier the enrollment, the lower the loss-of-LE, namely, 0.06±0.72 years for interval <1 year, 0.05±0.59 years for interval 1-4 years, 10.01±0.11 years for interval 5-9 years, and 12.77±0.14 years for interval 10-15 years, respectively (P<0.001), compared with 2.60±0.14 years for non-P4P group.</p><p><strong>Conclusion: </strong>Early enrollment in the P4P program was associated with reduced loss-of-LE, indicating P4P might gain life if implemented early after diabetes diagnosis.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat.","authors":"Serena Boccella, Andrea Maria Morace, Cristina Giorgio, Francesca Guida, Michela Perrone, Iolanda Manzo, Carmela Belardo, Meghan Jones, Sabatino Maione, Andrea Aramini, Marcello Allegretti, Livio Luongo, Laura Brandolini","doi":"10.4093/dmj.2024.0504","DOIUrl":"https://doi.org/10.4093/dmj.2024.0504","url":null,"abstract":"<p><strong>Background: </strong>The CXC motif chemokine ligand 8 (CXCL8)-CXC motif chemokine receptor 1/2 (CXCR1/2) axis has been implicated in type 1 diabetes mellitus (T1DM). Its actions on non-immune cells may also contribute to T1DM-associated complications, including painful diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR).</p><p><strong>Methods: </strong>We assessed the efficacy of early (4-8 weeks) or late (8-12 weeks) daily ladarixin (LDX) for the treatment of streptozotocin (STZ)-induced T1DM and the related complications of DPN or DR in male rats.</p><p><strong>Results: </strong>Early LDX mitigated STZ-induced dysmetabolism (i.e., blood glucose, insulin), inflammation in dorsal root ganglion/ sciatic nerve (interleukin-1β and tumor necrosis factor-α expression) and mechanical allodynia and thermal hyperalgesia, indicative of DPN. Moreover, vitreous citrullinated histone H3 (CitH3) and plasma GRO/CINC1 (CXCL8) increase were attenuated. Late LDX failed to reverse STZ-induced changes in metabolic parameters (i.e., blood glucose, insulin, C-peptide, pancreatic β-cell number and function). Strikingly, even in the absence of an effect on glycemic control, late LDX mitigated STZ-induced mechanical allodynia and thermal hyperalgesia and vitreous (CXCL8, CitH3) and retinal (CXCL8, CXCR1/2, myeloperoxidase, CitH3) inflammatory/pro-angiogenic (vascular endothelial growth factor, CD34) signs of DR.</p><p><strong>Conclusion: </strong>These data confirm the efficacy of LDX in STZ-induced T1DM and provide evidence of a protective effect also against DPN and onset of DR which is independent of its effect on β-cell functionality preservation and glycemic control.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, Regional, and National Temporal Trends in Incidence for Type 2 Diabetes Mellitus Related Chronic Kidney Disease from 1992 to 2021.","authors":"Yu Cao, Huiting Chen, Hui Liu, Hao Wu, Wei Gao","doi":"10.4093/dmj.2024.0593","DOIUrl":"https://doi.org/10.4093/dmj.2024.0593","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is a major cause of declining renal function.</p><p><strong>Methods: </strong>Temporal trends in T2DM-related chronic kidney disease (CKD-T2DM) incidence across 204 countries and territories from 1992 to 2021 were analyzed using data from the Global Burden of Disease 2021. The impact of macro-factors (demographic change, age, period, and birth cohort) on CKD-T2DM incidence trends was assessed using decomposition analyses and age-period- cohort modeling, highlighting opportunities to improve incidence and reduce regional disparities.</p><p><strong>Results: </strong>In 2021, global CKD-T2DM incidence cases reached 2.01 million, a 150.92% increase since 1992, with population growth and aging contributing to 80% of this rise. The age-standardized incidence rate (ASIR) ranged from 15.09 per 100,000 in low sociodemographic index (SDI) regions to 23.07 in high SDI regions. China, India, the United States, and Japan have the most incidence cases, accounted for 69% of incidence cases globally. With 175 countries showing an increasing ASIR trend. Unfavorable trend in ASIR increase were generally found in most high-middle and middle SDI countries, such as China and Mexico (net drift=0.15% and 1.17%, per year). Age-period-cohort analyses indicated a high incidence risk near age 80, with worsening risks for recent periods and birth cohorts, except in high SDI areas.</p><p><strong>Conclusion: </strong>The CKD-T2DM incidence burden continues to rise globally, with significant variations between countries, posing major global health implications. CKD-T2DM is largely preventable and treatable, warranting greater attention in global health policy, particularly for older populations and in low and middle SDI regions.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-Specific Progranulin Deficiency Prevents Diet-Induced Obesity through the Inhibition of Hypothalamic and Adipose Tissue Inflammation.","authors":"Chan Hee Lee, Chae Beom Park, Hyun-Kyong Kim, Won Hee Jang, Se Hee Min, Jae Bum Kim, Min-Seon Kim","doi":"10.4093/dmj.2024.0486","DOIUrl":"https://doi.org/10.4093/dmj.2024.0486","url":null,"abstract":"<p><strong>Background: </strong>Chronic low-grade inflammation in multiple metabolic organs contributes to the development of insulin resistance induced by obesity. Progranulin (PGRN) is an evolutionarily-conserved secretory protein implicated in immune modulation. The generalized deletion of the PGRN-encoded Grn gene improves insulin resistance and glucose intolerance in obese mice fed a high-fat diet (HFD). However, it remains unclear which cells or organs are responsible for the beneficial metabolic effect of Grn depletion.</p><p><strong>Methods: </strong>Considering the critical role of macrophages in HFD-induced obesity and inflammation, we generated mice with a macrophage-specific Grn depletion (Grn-MΦKO mice) by mating lysozyme M (LysM)-Cre and Grn-floxed mice. Body weight, food intake, energy expenditure, and glucose and insulin tolerance were compared between Grn-MΦKO mice and their wildtype (WT) controls under normal chow diet (NCD)- or HFD-fed conditions. We also examined macrophage activation and inflammation- related gene expression in the visceral adipose tissue and hypothalamus along with insulin and leptin signaling.</p><p><strong>Results: </strong>Grn-MΦKO mice showed no alteration in metabolic phenotypes under NCD-fed conditions. However, upon HFD feeding, these mice exhibited less weight gain and improved glucose and insulin tolerance compared to WT mice. Moreover, HFD-induced macrophage activation and proinflammatory cytokine expression were significantly reduced in both the adipose tissue and hypothalamus of Grn-MΦKO mice, while HFD-induced impairments in leptin and insulin signaling showed improvement.</p><p><strong>Conclusion: </strong>Macrophage-derived PGRN and possibly other Grn products play a critical role in the development of HFD-induced obesity, tissue inflammation, and impaired hormonal signaling in both central and peripheral metabolic organs.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}