Nutrition & Diabetes最新文献

{"title":"A mixed meal tolerance test predicts onset of type 2 diabetes in Southwestern Indigenous adults.","authors":"Cassie M Mitchell, Emma J Stinson, Douglas C Chang, Jonathan Krakoff","doi":"10.1038/s41387-024-00269-3","DOIUrl":"10.1038/s41387-024-00269-3","url":null,"abstract":"<p><strong>Background/objective: </strong>To identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT).</p><p><strong>Methods: </strong>Adult Indigenous Americans without diabetes (n = 501) from a longitudinal cohort underwent at baseline a 4-h MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by the total and incremental area under the curve (AUC/iAUC).</p><p><strong>Results: </strong>At follow-up (median time 9.6 [inter-quartile range: 5.6-13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC_180-min (HR: 1.98, 95% CI: 1.67, 2.34, p < 0.0001), AUC_240-min (HR: 1.93, 95% CI: 1.62, 2.31, p < 0.0001), and iAUC_180-min (HR: 1.43, 95% CI: 1.20, 1.71, p < 0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC_180-min (HR: 1.44, 95% CI: 1.10, 1.88, p = 0.007) and AUC_240-min (HR: 1.41, 95% CI: 1.09, 1.84, p < 0.01) remained associated with increased risk of diabetes.</p><p><strong>Conclusions: </strong>Glucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk.</p><p><strong>Clinical trial registry: </strong>ClinicalTrials.gov identifier : NCT00340132, NCT00339482.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the association between vitamin D and prediabetes in adults: A cross-sectional study.","authors":"Ali H Ziyab, Anwar Mohammad, Zainab Almousa, Talal Mohammad","doi":"10.1038/s41387-024-00311-4","DOIUrl":"10.1038/s41387-024-00311-4","url":null,"abstract":"<p><strong>Background/objectives: </strong>Vitamin D status has been shown to be associated with prediabetes risk. However, epidemiologic evidence on whether sex modulates the association between vitamin D and prediabetes is limited. The present study investigated sex-specific associations between vitamin D and prediabetes.</p><p><strong>Subjects/methods: </strong>The Kuwait Wellbeing Study, a population-based cross-sectional study, enrolled nondiabetic adults. Prediabetes was defined as 5.7 ≤ HbA1c% ≤6.4; 25-hydroxyvitamin D (25(OH)D) was measured in venous blood and analyzed as a continuous, dichotomous (deficiency: <50 nmol/L vs. insufficiency/sufficiency ≥50 nmol/L), and categorical (tertiles) variable. Associations were evaluated by estimating adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), while stratifying by sex.</p><p><strong>Results: </strong>A total of 384 participants (214 males and 170 females) were included in the current analysis, with a median age of 40.5 (interquartile range: 33.0-48.0) years. The prevalence of prediabetes was 35.2%, and 63.0% of participants had vitamin D deficiency. Assessments of statistical interaction between sex and 25(OH)D status were statistically significant (P_{Sex × 25(OH)D Interaction} < 0.05). In the sex-stratified analysis, after adjustment for confounding factors, decreased 25(OH)D levels were associated with increased prevalence of prediabetes in males (aPR_{Deficiency vs. In-/Sufficiency}: 2.35, 95% CI: 1.36-4.07), but not in females (aPR_{Deficiency vs. In-/Sufficiency}: 1.03, 95% CI: 0.60-1.77). Moreover, the prevalence of prediabetes differed between males and females at 25(OH)D levels of ≤35 nmol/L, with a higher prevalence of prediabetes in males compared to females. Such a sex-specific difference was not observed at 25(OH)D levels of >35 nmol/L.</p><p><strong>Conclusions: </strong>Sex modified the association between vitamin D levels and prediabetes, with an inverse association observed among males, but not among females. Moreover, the observed sex-disparity in the prevalence of prediabetes was only pronounced at 25(OH)D levels of ≤35 nmol/L.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-trimester hemoglobin, haptoglobin genotype, and risk of gestational diabetes mellitus in a retrospective study among Chinese pregnant women.","authors":"Yue Li, Fang Wang, Xinmei Huang, Shuhang Zong, Yi Shen, Lina Guo, Qiongyi Cai, Tiange Sun, Rui Zhang, Zhiyan Yu, Liwen Zhang, Shufei Zang, Jun Liu","doi":"10.1038/s41387-024-00309-y","DOIUrl":"10.1038/s41387-024-00309-y","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk.</p><p><strong>Methods: </strong>This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk.</p><p><strong>Results: </strong>Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk.</p><p><strong>Conclusion: </strong>Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of basic carbohydrate counting versus standard dietary care for glycaemic control in type 2 diabetes (The BCC Study): a randomised, controlled trial.","authors":"Bettina Ewers, Martin B Blond, Jens M Bruun, Tina Vilsbøll","doi":"10.1038/s41387-024-00307-0","DOIUrl":"10.1038/s41387-024-00307-0","url":null,"abstract":"<p><strong>Background: </strong>Clinical guidelines recommend basic carbohydrate counting (BCC), or similar methods to improve carbohydrate estimation skills and to strive for higher consistency in carbohydrate intake potentially improving glycaemic control. However, evidence for this approach in type 2 diabetes (T2D) is limited.</p><p><strong>Objective: </strong>To examine the efficacy of a structured education program in BCC as add-on to standard dietary care on glycaemic control in individuals with T2D.</p><p><strong>Methods: </strong>The BCC Study was a randomized, controlled, open-label, parallel-group trial. Individuals with T2D aged 18-75 years with glycated haemoglobin A1c (HbA1c) 53-97 mmol/mol (7.0-11.0%) were randomly assigned (1:1) to BCC or standard dietary care. The primary outcomes were differences in changes in HbA1c or glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) between groups after six months of intervention.</p><p><strong>Results: </strong>Between September 2018 and July 2021, 48 participants were randomly assigned, 23 to BCC and 25 to standard dietary care. Seven participants did not receive the allocated intervention. From a baseline-adjusted mean of 65 mmol/mol (95% CI 62-68 [8.1%, 7.8-8.4]), HbA1c changed by -5 mmol/mol (-8 to -1 [-0.5%, -0.7 to -0.1]) in BCC and -3 mmol/mol (-7 to 1 [-0.3%, -0.6 to 0.1]) in standard care with an estimated treatment effect of -2 mmol/mol (-7 to 4 [-0.2%, -0.6 to 0.4]); p = 0.554. From a baseline-adjusted mean of 4.2 mmol/l (3.7 to 4.8), MAGE changed by -16% (-33 to 5) in BCC and by -3% (-21 to 20) in standard care with an estimated treatment effect of -14% (-36 to 16); p = 0.319. Only median carbohydrate estimation error in favour of BCC (estimated treatment difference -55% (-70 to -32); p < 0.001) remained significant after multiple testing adjustment.</p><p><strong>Conclusions: </strong>No glycaemic effects were found but incorporating BCC as a supplementary component to standard dietary care led to improved skills in estimating carbohydrate intake among individuals with T2D.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary resistant starch enhances immune health of the kidney in diabetes via promoting microbially-derived metabolites and dampening neutrophil recruitment.","authors":"Matthew Snelson, Devy Deliyanti, Sih Min Tan, Anna M Drake, Cassandra de Pasquale, Vinod Kumar, Trent M Woodruff, Jennifer L Wilkinson-Berka, Melinda T Coughlan","doi":"10.1038/s41387-024-00305-2","DOIUrl":"10.1038/s41387-024-00305-2","url":null,"abstract":"<p><strong>Background: </strong>Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated.</p><p><strong>Methods: </strong>Six-week-old db/db mice were fed a diet containing 12.5% resistant starch or a control diet matched for equivalent regular starch for 10 weeks. db/m mice receiving the control diet were utilised as non-diabetic controls. Freshly collected kidneys were digested for flow cytometry analysis of immune cell populations. Kidney injury was determined by measuring albuminuria, histology, and immunohistochemistry. Portal vein plasma was collected for targeted analysis of microbially-derived metabolites. Intestinal histology and tight junction protein expression were assessed.</p><p><strong>Results: </strong>Resistant starch limited the development of albuminuria in db/db mice. Diabetic db/db mice displayed a decline in portal vein plasma levels of acetate, propionate, and butyrate, which was increased with resistant starch supplementation. Diabetic db/db mice receiving resistant starch had a microbially-derived metabolite profile similar to that of non-diabetic db/m mice. The intestinal permeability markers lipopolysaccharide and lipopolysaccharide binding protein were increased in db/db mice consuming the control diet, which was not seen in db/db mice receiving resistant starch supplementation. Diabetes was associated with an increase in the kidney neutrophil population, neutrophil activation, number of C5aR1+ neutrophils, and urinary complement C5a excretion, all of which were reduced with resistant starch. These pro-inflammatory changes appear independent of fibrotic changes in the kidney.</p><p><strong>Conclusions: </strong>Resistant starch supplementation in diabetes promotes beneficial circulating microbially-derived metabolites and improves intestinal permeability, accompanied by a modulation in the inflammatory profile of the kidney including neutrophil infiltration, complement activation, and albuminuria. These findings indicate that resistant starch can regulate immune and inflammatory responses in the kidney and support the therapeutic potential of resistant starch supplementation in diabetes on kidney health.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes","authors":"Zhang Xia, Shulong Shi, Xiaoqing Ma, Feng Li, Xinya Li, Herbert Y. Gaisano, Mingyang Zhao, Yuhao Li, Yan He, Jiajia Jiang","doi":"10.1038/s41387-024-00302-5","DOIUrl":"https://doi.org/10.1038/s41387-024-00302-5","url":null,"abstract":"","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141335117","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":"Correction: Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial.","authors":"Alicia Podadera-Herreros, Antonio P Arenas-de Larriva, Francisco M Gutierrez-Mariscal, Juan F Alcala-Diaz, Ana Ojeda-Rodriguez, Fernando Rodriguez-Cantalejo, Magdalena P Cardelo, Diego Rodriguez-Cano, Jose D Torres-Peña, Raul M Luque, Jose M Ordovas, Pablo Perez-Martinez, Javier Delgado-Lista, Jose Lopez-Miranda, Elena M Yubero-Serrano","doi":"10.1038/s41387-024-00304-3","DOIUrl":"10.1038/s41387-024-00304-3","url":null,"abstract":"","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-valine is a powerful stimulator of GLP-1 secretion in rodents and stimulates secretion through ATP-sensitive potassium channels and voltage-gated calcium channels.","authors":"Ida Marie Modvig, Mark M Smits, Katrine Douglas Galsgaard, Anna Pii Hjørne, Anna Katarzyna Drzazga, Mette Marie Rosenkilde, Jens Juul Holst","doi":"10.1038/s41387-024-00303-4","DOIUrl":"10.1038/s41387-024-00303-4","url":null,"abstract":"<p><strong>Background: </strong>We previously reported that, among all the naturally occurring amino acids, L-valine is the most powerful luminal stimulator of glucagon-like peptide 1 (GLP-1) release from the upper part of the rat small intestine. This makes L-valine an interesting target for nutritional-based modulation of GLP-1 secretion. However, the molecular mechanism of L-valine-induced secretion remains unknown.</p><p><strong>Methods: </strong>We aimed to investigate the effect of orally given L-valine in mice and to identify the molecular details of L-valine stimulated GLP-1 release using the isolated perfused rat small intestine and GLUTag cells. In addition, the effect of L-valine on hormone secretion from the distal intestine was investigated using a perfused rat colon.</p><p><strong>Results: </strong>Orally given L-valine (1 g/kg) increased plasma levels of active GLP-1 comparably to orally given glucose (2 g/kg) in male mice, supporting that L-valine is a powerful stimulator of GLP-1 release in vivo (P > 0.05). Luminal L-valine (50 mM) strongly stimulated GLP-1 release from the perfused rat small intestine (P < 0.0001), and inhibition of voltage-gated Ca²⁺-channels with nifedipine (10 μM) inhibited the GLP-1 response (P < 0.01). Depletion of luminal Na⁺ did not affect L-valine-induced GLP-1 secretion (P > 0.05), suggesting that co-transport of L-valine and Na⁺ is not important for the depolarization necessary to activate the voltage-gated Ca²⁺-channels. Administration of the K_ATP-channel opener diazoxide (250 μM) completely blocked the L-valine induced GLP-1 response (P < 0.05), suggesting that L-valine induced depolarization arises from metabolism and opening of K_ATP-channels. Similar to the perfused rat small intestine, L-valine tended to stimulate peptide tyrosine-tyrosine (PYY) and GLP-1 release from the perfused rat colon.</p><p><strong>Conclusions: </strong>L-valine is a powerful stimulator of GLP-1 release in rodents. We propose that intracellular metabolism of L-valine leading to closure of K_ATP-channels and opening of voltage-gated Ca²⁺-channels are involved in L-valine induced GLP-1 secretion.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alantolactone attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.","authors":"Jiong Wang, Yucheng Jiang, Leiming Jin, Chenchen Qian, Wei Zuo, Jianjun Lin, Longteng Xie, Bo Jin, Yanni Zhao, Lijiang Huang, Yi Wang","doi":"10.1038/s41387-024-00300-7","DOIUrl":"10.1038/s41387-024-00300-7","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with an increasing incidence, which can further develop into liver fibrosis and hepatocellular carcinoma at the end stage. Alantolactone (Ala), a sesquiterpene lactone isolated from Asteraceae, has shown anti-inflammatory effects in different models. However, the therapeutic effect of Ala on NAFLD is not clear.</p><p><strong>Methods: </strong>C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD. After 16 weeks, Ala was administered by gavage to observe its effect on NAFLD. RNA sequencing of liver tissues was performed to investigate the mechanism. In vitro, mouse cell line AML-12 was pretreated with Ala to resist palmitic acid (PA)-induced inflammation, oxidative stress and fibrosis.</p><p><strong>Results: </strong>Ala significantly inhibited inflammation, fibrosis and oxidative stress in HFD-induced mice, as well as PA-induced AML-12 cells. Mechanistic studies showed that the effect of Ala was related to the induction of Nrf2 and the inhibition of NF-κB. Taken together, these findings suggested that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress.</p><p><strong>Conclusions: </strong>The study found that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress, suggesting that Ala is an effective therapy for NAFLD.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D is involved in the effects of the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys in mice with DKD.","authors":"Xiaodi Zheng, Yuhong Huang, Mengxue Yang, Lulu Jin, Xuemeng Zhang, Rui Zhang, Yueyue Wu, Cuili Yan, Yuan Gao, Miao Zeng, Fei Li, Xue Zhou, Neng Zhang, Jun Liu, Bingbing Zha","doi":"10.1038/s41387-024-00297-z","DOIUrl":"10.1038/s41387-024-00297-z","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear.</p><p><strong>Methods: </strong>DKD mice were received different concentrations of 1,25-(OH)₂D₃ for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney.</p><p><strong>Results: </strong>1,25-(OH)₂D₃ could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR.</p><p><strong>Conclusions: </strong>The protective effect of 1,25-(OH)₂D₃ in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}