{"title":"Characteristic external genitalia in male neonates with 5α-reductase deficiency.","authors":"Takeshi Munenaga, Yosuke Ichihashi, Satsuki Nakano, Hironori Shibata, Takeshi Sato, Hiroshi Asanuma, Keiko Homma, Tomonobu Hasegawa, Tomohiro Ishii","doi":"10.1507/endocrj.EJ23-0740","DOIUrl":"10.1507/endocrj.EJ23-0740","url":null,"abstract":"<p><p>There have been no reports comparing neonatal external genitalia of 5α-reductase deficiency (5αRD) with those of other 46,XY differences of sex differentiation (DSD). This study enrolled 31 Japanese cases of 46,XY DSD whose external genitalia was examined during the neonatal period; four were diagnosed as 5αRD and 15 were defined as non-5αRD by genetic analysis of SRD5A2 or urinary steroid metabolites. We compared the following characteristics between 5αRD and non-5αRD groups, adjusting the severity of undermasculinization of the external genitalia: stretched penile length (SPL), glans width, location of the external urethral opening, and proportion of undescended testis. The external genitalia of all the 5αRD cases were Quigley classification grade 2 or 3. We compared the phenotypes between the four 5αRD cases and 11 non-5αRD cases with grade 2 or 3. The median (range) of SPL in the 5αRD group (14 mm [11-16]) was significantly lower than that in the non-5αRD group (22 mm [15-29]) (p = 0.003). An SPL cut-off value of <15 mm yielded a sensitivity of 50% (95% confidence interval [CI]; 7-93%) and specificity of 100% (95% CI, 72-100%) for discriminating between the groups. The median glans width, location of the external urethral opening, and proportion of undescended testis were not significantly different between the groups. The SPL of 5αRD in Quigley classification grade 2 or 3 was significantly shorter than that of other 46,XY DSDs with the equivalent grade.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"973-978"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endocrine journalPub Date : 2024-10-01DOI: 10.1507/endocrj.EJ24-0194
Takahiro Inaishi, Dai Takeuchi, Takahiro Ichikawa, Gai Inaguma, Atsushi Hashizume, Masaki Okazaki, Norikazu Masuda, Toyone Kikumori
{"title":"Impact of periodic neck ultrasonography on locoregional disease control in surveillance after total thyroidectomy for patients with low- and intermediate-risk papillary thyroid carcinoma: a propensity score-matched study.","authors":"Takahiro Inaishi, Dai Takeuchi, Takahiro Ichikawa, Gai Inaguma, Atsushi Hashizume, Masaki Okazaki, Norikazu Masuda, Toyone Kikumori","doi":"10.1507/endocrj.EJ24-0194","DOIUrl":"https://doi.org/10.1507/endocrj.EJ24-0194","url":null,"abstract":"<p><p>This study aimed to evaluate the impact of periodic neck ultrasonography (US) on postoperative surveillance for locoregional disease control of patients with low- and intermediate-risk papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. This retrospective cohort study included patients with PTC who underwent total thyroidectomy and central neck dissection at our institution between January, 2000 and December, 2016. The patients were divided into two groups: the physical examination (PE) group (follow-up by PE without periodic US) and the US group (follow-up by PE with periodic US). Serum thyroglobulin levels were measured periodically in both groups. Propensity score matching was used to rigorously balance the significant variables and assess the 10-year postoperative outcomes between the groups. Of the 189 patients, 150 were included after matching (75 in each group). There were no significant differences between the two groups in terms of background characteristics. The median follow-up period was 127.9 months. There was no significant difference in locoregional relapse-free survival between the PE and US groups (97.0 vs. 98.7%, p = 0.541). The overall survival was 96.7% and 98.7% in the PE and US groups, respectively, with no significant difference (p = 0.364). This study demonstrated that the addition of periodic US to PE for postoperative surveillance of patients with low- and intermediate-risk PTC who underwent total thyroidectomy did not significantly affect locoregional control.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endocrine journalPub Date : 2024-10-01Epub Date: 2024-07-10DOI: 10.1507/endocrj.EJ23-0725
Hideyasu Asai, Ikuo Yamamori, Shigeru Hagimoto, Kyoichi Okumura, Koki Sakakibara
{"title":"Cushing's disease with twin pregnancy and diabetes mellitus: a case report and literature review.","authors":"Hideyasu Asai, Ikuo Yamamori, Shigeru Hagimoto, Kyoichi Okumura, Koki Sakakibara","doi":"10.1507/endocrj.EJ23-0725","DOIUrl":"10.1507/endocrj.EJ23-0725","url":null,"abstract":"<p><p>A 38-year-old Japanese woman with a history of abnormal thyroid function of non-autoimmune origin, pituitary endocrine tumor, and untreated diabetes mellitus was referred to our outpatient clinic when she became pregnant with twins. Physical findings consistent with Cushing's syndrome (CS) were absent at the time of presentation. Although baseline plasma adrenocorticotropic hormone, serum cortisol, and 24-hour urinary free cortisol excretion levels were above the upper limits of normal non-pregnant reference ranges, we could not exclude a physiological increase associated with pregnancy. No medical or surgical intervention for hypercortisolism was performed during pregnancy. Spontaneous vaginal delivery resulted in the normal delivery of live twins. A diagnosis of Cushing's disease (CD) was established when papery skin developed postpartum. Transsphenoidal surgery was performed and the hypercortisolism partially resolved post-operatively. The patient's abnormal thyroid function also resolved. Pregnancy in women with endogenous CS is rare, with less than 300 cases reported. Most reported cases of CS during pregnancy are of adrenal origin. Only two cases of twin pregnancies with CD have been reported. Therefore, we reported the third case of CD in a twin pregnancy and reviewed the diagnostic and therapeutic challenges associated with CD during pregnancy.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"1003-1011"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endocrine journalPub Date : 2024-10-01Epub Date: 2024-07-06DOI: 10.1507/endocrj.EJ24-0193
Kosuke Inoue
{"title":"Causal inference and machine learning in endocrine epidemiology.","authors":"Kosuke Inoue","doi":"10.1507/endocrj.EJ24-0193","DOIUrl":"10.1507/endocrj.EJ24-0193","url":null,"abstract":"<p><p>With the rapid development of computer science, there is an increasing demand for the use of causal inference methods and machine learning in the research of endocrine disorders and their long-term health outcomes. However, studies on the effective and appropriate applications of these approaches in real-world data and clinical settings are still limited. This review will illustrate the use of causal inference and machine learning in epidemiological research within the field of endocrinology and metabolism. It will examine each concept of causal inference and machine learning through application examples of endocrine disorders. Subsequently, the paper will discuss the integration of machine learning within the causal inference framework, including (i) the estimation of treatment effects or the causal relationship between exposure and outcomes, and (ii) the evaluation of heterogeneity in such treatment effects (or exposure-outcome causal relationship) based on individuals' characteristics. Accurately assessing causal relationships and their heterogeneity across different individuals is crucial not only for determining effective interventions, but also for the appropriate allocation of medical resources and reducing healthcare disparities. By illustrating some application examples in endocrinology, this review aims to enhance readers' understanding and application of causal inference and machine learning in future epidemiological studies focusing on endocrine disorders.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"945-953"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transition from hypothyroidism to Graves' disease, development of thyroid eye disease, progression to optic neuropathy after inpatient pulse therapy, and long-term administration of outpatient pulse therapy: a case report with review of literature.","authors":"Koichiro Mizuochi, Yuji Hiromatsu, Yui Nakamura, Aya Sonezaki, Ayaka Adachi, Tamotsu Kato, Nobuhiko Wada, Tomohiro Kurose, Shiho Watanabe","doi":"10.1507/endocrj.EJ24-0347","DOIUrl":"https://doi.org/10.1507/endocrj.EJ24-0347","url":null,"abstract":"<p><p>A 55-year-old woman transitioned from hypothyroidism to Graves' disease (GD) and then developed thyroid eye disease (TED) with proptosis and diplopia. After three cycles of daily methylprednisolone pulse therapy, her condition progressed to dysthyroid optic neuropathy with decreased visual acuity in both eyes. Her clinical activity score (CAS) was 7 points. Orbital magnetic resonance imaging (MRI) showed that the enlarged extraocular muscles were compressing the optic nerve in the area of the cones. Although her visual acuity recovered during two further cycles of daily pulse therapy, disease activity persisted for 4 years. TED exacerbated five times. Each time, the patient received weekly pulse therapy with no adverse reactions until her ophthalmopathy was relieved. The total cumulative dose of methylprednisolone was 59.5 g. Thyroid-stimulating antibody (TSAb) was positive from the time of hypothyroidism onset and became strongly positive with the onset of GD and the progress of TED. In addition, MRI was useful for the evaluation of the pathophysiology of ophthalmopathy. This case report suggests that careful monitoring by both endocrinologists and ophthalmologists using CAS, ophthalmological assessments, TSAb measurement, and orbital MRI are useful for making treatment decisions for TED.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential implications of thyroid autoantibodies in children, adolescents, and young adults with thyroid nodules in Japan: The Fukushima Health Management Survey.","authors":"Rina Tazaki, Yurie Kobashi, Nana Nakahata, Mahiro Asano, Norikazu Abe, Haruka Ejiri, Ayako Sato, Natsuki Nagamine, Chisato Takahashi, Yukie Yamaya, Manabu Iwadate, Takashi Matsuzuka, Satoshi Suzuki, Tetsuya Ohira, Satoru Suzuki, Fumihiko Furuya, Hiroki Shimura, Shinichi Suzuki, Susumu Yokoya, Shunichi Yamashita, Hitoshi Ohto, Seiji Yasumura","doi":"10.1507/endocrj.EJ24-0293","DOIUrl":"https://doi.org/10.1507/endocrj.EJ24-0293","url":null,"abstract":"<p><p>There have been no systematic epidemiological evaluations of the relationship between thyroid autoimmunity and the clinical background of young patients with thyroid nodules. We aimed to clarify the clinical features associated with thyroglobulin or thyroperoxidase antibodies (thyroid autoantibodies [Tabs]) in children and young adults with nodules. We performed a cross-sectional study using data from 3,018 participants of 3-29 years of age with nodules, including thyroid cancer, from the Fukushima Health Management Survey. After stratification of the data for body mass index (BMI) and the bilateral width and thickness of the area (BWTAR) as indicators of thyroid volume for age, sex, body surface area (BSA), and sex-adjusted standard deviation score (SDS), trend analyses were performed. A logistic regression analysis was performed using tab-positivity as an objective variable. The overall prevalence of tab-positivity is 13.9%. It was high in females (17%), participants with diffuse goiter (DG) (19.2%), and those with papillary thyroid carcinoma (PTC) (12.8%). The age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS, BWTAR-SDS, presence of DG, diagnosis of PTC, and TSH concentrations were 0.962 (0.863-1.073), 1.263 (1.171-1.361), 7.357 (4.816-11.239), 2.787 (1.965-4.014), and 1.403 (1.257-1.564), respectively. Tab positivity was independently associated with a large thyroid, the presence of DG, the presence of PTC, and a high TSH concentration in patients with nodules. Based on the systematic epidemiologic evidence shown in young patients, Tab positivity might complement ultrasonography for the assessment of the thyroid function and identification of malignancy in younger patients with asymptomatic thyroid nodules.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between non-high-density lipoprotein cholesterol and type 2 diabetes: a systematic review and meta-analysis of cohort studies.","authors":"Mengqi Han, Yue Shen, Xin Guo, Cheng Hong, Xincan Ji, Haoyang Guo, Yuelong Jin, Hui Yuan","doi":"10.1507/endocrj.EJ24-0189","DOIUrl":"https://doi.org/10.1507/endocrj.EJ24-0189","url":null,"abstract":"<p><p>Non-high-density lipoprotein cholesterol (non-HDL), a more readily available and reliable lipid parameter, is unclear in its association with type 2 diabetes (T2D). Previous studies assessing the relationship between non-HDL and T2D risk remains inconsistent results. We performed a meta-analysis to systematically evaluate this association. The PubMed, EMBASE, Medline, Web of Science, and Cochrane Library databases were systematically searched to find articles on \"non-HDL\" and \"T2D\" from inception to December 6, 2023. A random-effects model was used to calculate the effect estimates and 95% confidence intervals. Subgroup analyses and univariate Meta-regression were performed to explore sources of heterogeneity. The main exposure and outcome were non-HDL and T2D, respectively, in the general population. A total of 8 studies included 251,672 participants who met the inclusion criteria for this study. Meta-analysis showed that higher non-HDL increased the risk of T2D compared with the lower non-HDL group (total effect size: 1.16; 95% CI 1.079-1.251, p < 0.001). Subgroup analyses and Meta-regression of the association between non-HDL and T2D were not affected by region, proportion of men, sample size, or adjustment for confounders (including BMI, hypertension, waist circumference, and family history of diabetes). Higher non-HDL may be associated with an increased risk of T2D. Large prospective cohort studies are needed to validate these findings, and further studies are required in order to elucidate the underlying pathophysiologic mechanisms underlying the association between non-HDL and T2D.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endocrine journalPub Date : 2024-09-14DOI: 10.1507/endocrj.ej24-0256
Chenxi Yang, Yi Chen, Guangfeng Tang, Tongtong Shen, Li Li
{"title":"Dysregulation of c-Jun (JUN) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) in obese people and their predictive values for metabolic syndrome","authors":"Chenxi Yang, Yi Chen, Guangfeng Tang, Tongtong Shen, Li Li","doi":"10.1507/endocrj.ej24-0256","DOIUrl":"https://doi.org/10.1507/endocrj.ej24-0256","url":null,"abstract":"</p><p>The incidences of metabolic syndrome (MetS), denoting insulin resistance-associated various metabolic disorders, are increasing. This study aimed to identify new biomarkers for predicting MetS and provide a novel diagnostic approach. Herein, the expression profiles of c-Jun (JUN) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) in individuals with obesity and patients with MetS from the Gene Expression Omnibus database. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the messenger RNA levels of JUN and FOSB in the peripheral blood of healthy volunteers (lean and obese) and patients with MetS (lean and obese), along with that in the adipose tissue and peripheral blood of obese mouse model. Furthermore, receiver operating characteristic (ROC) curve and logistic regression analyses were performed to determine the diagnostic value of JUN and FOSB in MetS. The expression profiles and RT-qPCR results showed that JUN and FOSB were highly expressed in individuals with obesity, obese mouse models, and patients with MetS. The ROC analysis results showed an area under the curve values of 0.872 and 0.879 for JUN, 0.802 and 0.962 for FOSB, and 0.946 and 0.979 for JUN–FOSB in the lean group and the group with obesity, respectively, in predicting MetS. Logistic regression analysis showed that the <i>p</i>-values of both JUN and FOSB as MetS-affecting factors were <0.05. Altogether, the findings of this study indicate that both JUN and FOSB, abnormally expressed in individuals with obesity, are good biomarkers of MetS.</p>\u0000<p></p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":"15 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endocrine journalPub Date : 2024-09-12DOI: 10.1507/endocrj.ej24-0164
Yan Wang, Caiyuan Yu, Xiaoyan Zheng, Yaya Wang, Wei Zhang
{"title":"Effects of dipeptidyl peptidase 4 inhibitors on the risk of acute respiratory failure in patients with type 2 diabetes mellitus: a meta-analysis of cardiovascular outcomes trials","authors":"Yan Wang, Caiyuan Yu, Xiaoyan Zheng, Yaya Wang, Wei Zhang","doi":"10.1507/endocrj.ej24-0164","DOIUrl":"https://doi.org/10.1507/endocrj.ej24-0164","url":null,"abstract":"</p><p>Dipeptidyl peptidase 4 (DPP-4) inhibitors are new antidiabetic drugs. Their effects on the respiratory system remain unclear. This study aimed to determine the association between DDP-4 inhibitors and acute respiratory failure (ARF) among patients with type 2 diabetes mellitus (T2DM). A meta-analysis was performed by searching the PubMed, Embase, and CENTRAL databases up to July 3<sup>rd</sup>, 2024, to identify randomized controlled, double-blind, and placebo controlled-cardiovascular outcomes trials (CVOTs) that enrolled participants with T2DM. A total of 6,532 studies were initially retrieved; ultimately, 5 large CVOTs enrolling 47,714 adult T2DM patients were included in the meta-analysis. Overall, there were a nonsignificant increase in the risk of ARF in the DDP-4 inhibitor group compared with the placebo group (RR, 1.72; 95% CI, 0.59 to 4.97; <i>p</i> = 0.319). This is the first meta-analysis to evaluate the association between DDP-4 inhibitors and ARF among T2DM patients. In general, these findings suggest that DPP-4 inhibitors may slightly, but non-significantly, increase the risk of ARF in T2DM patients. As few studies are available and few ARF events occurred, further well-designed large-scale studies need to be performed.</p>\u0000<p></p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":"304 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tofogliflozin attenuates renal lipid deposition and inflammation via PPARα upregulation mediated by miR-21a impairment in diet-induced steatohepatitic mice","authors":"Sae Nishihara, Masahiro Koseki, Katsunao Tanaka, Takashi Omatsu, Ayami Saga, Hiroshi Sawabe, Hiroyasu Inui, Takeshi Okada, Tohru Ohama, Daisuke Okuzaki, Yoshihiro Kamada, Masafumi Ono, Makoto Nishida, Mikio Watanabe, Yasushi Sakata","doi":"10.1507/endocrj.ej24-0087","DOIUrl":"https://doi.org/10.1507/endocrj.ej24-0087","url":null,"abstract":"</p><p>We previously demonstrated hepatic, cardiac, and skin inflammation in a high-fat diet-induced steatotic liver disease (SLD) model. However, the molecular mechanism in the kidneys in this model remains unclear. It has been recently reported that SGLT2 inhibitors improve chronic kidney disease (CKD). Therefore, we used this model to evaluate the effects of tofogliflozin on renal lipid metabolism and inflammation. Male 8–10-week-old C57Bl/6 mice were fed a high-fat/high-cholesterol/high-sucrose/bile acid (HF/HC/HS/BA) diet with 0.015% tofogliflozin (Tofo group) or an HF/HC/HS/BA diet alone (SLD group). After eight weeks, serum lipid profiles, histology, lipid content, and mRNA/microRNA and protein expression levels in the kidney were examined. The Tofo group showed significant reductions in body (26.9 ± 0.9 <i>vs.</i> 24.5 ± 1.0 g; <i>p</i> < 0.001) and kidney weight compared to those of the SLD group. Renal cholesterol (9.1 ± 1.6 <i>vs.</i> 7.5 ± 0.7 mg/g; <i>p</i> < 0.05) and non-esterified fatty acid (NEFA) (12.0 ± 3.0 <i>vs.</i> 8.4 ± 1.5 μEq/g; <i>p</i> < 0.01) were significantly decreased in the Tofo group. Transmission electron microscopy revealed the presence of fewer lipid droplets. mRNA sequencing analysis revealed that fatty acid metabolism-related genes were upregulated and NFκB signaling pathway-related genes were downregulated in the Tofo group. MicroRNA sequencing analysis indicated that miR-21a was downregulated and miR-204 was upregulated in the Tofo group. Notably, the expression of PPARα, which has been known to be negatively regulated by miR-21, was significantly increased, leading to enhancing β-oxidation genes, <i>Acox1</i> and <i>Cpt1</i> in the Tofo group. Tofogliflozin decreased renal cholesterol and NEFA levels and improved inflammation through the regulation of PPARα and miR-21a.</p>\u0000<p></p>\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/endocrj/advpub/0/advpub_EJ24-0087/figure/advpub_EJ24-0087.jpg\"/>\u0000<span style=\"padding-left:5px;\">Fullsize Image</span>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":"56 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}