{"title":"The role of transient receptor potential melastatin channels in compressive force-induced contraction of primary cardiac pericytes.","authors":"Carmen Methner, Eugene Cilento, Zhiping Cao, Jeffrey Iliff, Anusha Mishra, Sanjiv Kaul","doi":"10.14814/phy2.70396","DOIUrl":"https://doi.org/10.14814/phy2.70396","url":null,"abstract":"<p><p>Pericytes contract during acute myocardial infarction (AMI) resulting in capillary constriction, which further contributes to the ischemic damage and enlargement of infarct size. We hypothesized that increased intramyocardial pressure during ischemia can be sensed by mechanosensitive Transient Receptor Potential (TRP) channels in cardiac pericytes, resulting in their contraction and worsening of myocardial necrosis during AMI. Here, we show that cultured primary cardiac pericytes express several TRP channels. Live-cell confocal imaging demonstrates that pharmacological stimulation with specific TRPM4 and TRPM7 agonists mobilizes cytosolic Ca<sup>2+</sup> within pericytes. Pressure stimulation (increased compressive forces) also increases pericyte Ca<sup>2+</sup>, which is abolished by specific TRPM4 and TRPM7 inhibitors. Lastly, we demonstrate that TRPM4 inhibition in vivo reduces infarct size by 3.5-fold in a rodent AMI model. We conclude that pericytes sense increased compressive forces (pressure) via TRPM channels both in vitro and in vivo. Inhibiting TRP channels may offer a therapeutic option to reduce infarct size in patients experiencing AMI.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 12","pages":"e70396"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fayez T Hammad, Loay Lubbad, Mariam Aljawder, Azza Al Ali, Suhail Al-Salam, Awwab F Hammad, Mustafa M Ardah, M Emdadul Haque, Jasmine Abdul Rasheed, Waheed F Hammad
{"title":"Does dihydromyricetin protect the kidney following ischemia-reperfusion injury in male rats?","authors":"Fayez T Hammad, Loay Lubbad, Mariam Aljawder, Azza Al Ali, Suhail Al-Salam, Awwab F Hammad, Mustafa M Ardah, M Emdadul Haque, Jasmine Abdul Rasheed, Waheed F Hammad","doi":"10.14814/phy2.70394","DOIUrl":"10.14814/phy2.70394","url":null,"abstract":"<p><p>Efforts to prevent the deleterious effects of the ischemia-reperfusion injury (IRI) on the kidney are ongoing. Recently, there has been an increasing interest in using natural phytochemical compounds as alternative remedies in several diseases. Dihydromyricetin is a flavonoid that is mainly extracted from some plants such as Ampelopsis grossedentata. The effect of dihydromyricetin was investigated in a rat model of renal IRI. Dihydromyricetin was dissolved in a vehicle and administered orally as a single daily dose of 400 mg/kg for 10 days prior to IRI and continued for 3 days after IRI. G-Sham (n = 10) underwent sham surgery, whereas G-IRI (n = 10) and G-IRI/DHM (n = 10) underwent bilateral warm renal ischemia for 35 min and received the vehicle or dihydromyricetin, respectively. Renal functions and histological changes were assessed before starting the medication, just prior to IRI, and 3 days after IRI. Dihydromyricetin significantly attenuated the alterations in serum creatinine and urea, creatinine clearance, urinary albumin, and urinary albumin creatinine ratio. Dihydromyricetin has also significantly mitigated the alterations in renal injury markers, pro-inflammatory, pro-fibrotic, and apoptotic cytokines, oxidative stress markers, and histological changes. We conclude that dihydromyricetin has a reno-protective effect on the IRI-induced renal alterations. These findings might have clinical implications.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 11","pages":"e70394"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benjamin R Tollitt, Samantha W Jones, Jessica Ohana, James R Henstock, Malcolm J Jackson, Anne McArdle
{"title":"A comparison of human skeletal muscle cell maturation in 2D versus 3D culture: A quantitative proteomic study.","authors":"Benjamin R Tollitt, Samantha W Jones, Jessica Ohana, James R Henstock, Malcolm J Jackson, Anne McArdle","doi":"10.14814/phy2.70420","DOIUrl":"10.14814/phy2.70420","url":null,"abstract":"<p><p>Compared with 2D monolayers, 3D models more closely mimic native muscle tissue and allow functional measurements. A more complete understanding of how culture conditions and duration affect myotube maturity/function is crucial for validating the transition to 3D systems. Human skeletal muscle cells were cultured as 2D monolayers or within 3D hydrogels for up to 21 days. Quantitative proteomic analysis and functional measurements were conducted to evaluate muscle cell differentiation. Myoblasts differentiated into myotubes by 8 days in both environments; however, at Day 8, 3D constructs exhibited a predominantly slow-twitch phenotype, compared with the mixed fiber type of 2D monolayers. By Day 21, 3D constructs demonstrated enhanced mitochondrial maturity, extracellular matrix remodeling, and a fast-twitch phenotype, indicated by increased myosin-2 abundance (Log2(FC)>1.29, p <0.05). Passive tension increased by >20% following prolonged culture of 3D muscle constructs, but contractile forces reduced by >40%. This study provides a comprehensive proteomic profile of human skeletal muscle cells in 2D and 3D, demonstrating that 3D culture promoted myotube maturity and highlighting the importance of selecting appropriate culture conditions. Data suggest 8 days of differentiation as ideal for achieving peak contractile force in 3D constructs, providing optimal models for testing interventions aimed at preserving muscle function.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 12","pages":"e70420"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leah J Mercier, Samantha J McIntosh, Joel S Burma, Julia Batycky, Julie M Joyce, Jean-Michel Galarneau, Michael J Esser, Kathryn J Schneider, Jonathan D Smirl, Sean P Dukelow, Ashley D Harris, Chantel T Debert
{"title":"Altered autonomic cardiovascular function in adults with persisting post-concussive symptoms and exercise intolerance.","authors":"Leah J Mercier, Samantha J McIntosh, Joel S Burma, Julia Batycky, Julie M Joyce, Jean-Michel Galarneau, Michael J Esser, Kathryn J Schneider, Jonathan D Smirl, Sean P Dukelow, Ashley D Harris, Chantel T Debert","doi":"10.14814/phy2.70378","DOIUrl":"10.14814/phy2.70378","url":null,"abstract":"<p><p>Alterations in autonomic cardiovascular function may result following mild traumatic brain injury (mTBI), but there is a lack of data evaluating autonomic function in adults with persisting post-concussive symptoms (PPCS). We collected resting measures of heart rate (HR), heart rate variability (HRV), blood pressure (BP) and cardiac baroreceptor sensitivity in 50 adults with PPCS (42.8 (11.0) years; 24.5 (14.2) months post-injury; 74% female) and 50 age/sex-matched controls (43.0 (11.1) years; 74% female) with no lifetime mTBI history. HR and BP data were collected for ≥4 min when seated and standing. Between-group differences (PPCS vs. control) were analyzed using linear regression. In the seated posture, participants with PPCS had significantly lower HRV than controls, specifically RMSSD (root mean squared of successive RR interval differences) (mean difference = -10.450, p = 0.001) and SDNN (standard deviation of RR intervals) (mean difference = -12.875, p = 0.001). In the standing position, PPCS had lower SDNN. Participants with PPCS had significantly lesser change in HRV, including RMSSD (mean difference = 5.981, p = 0.007) and LF/HF (low-frequency to high-frequency ratio) (mean difference = -2.229, p = 0.016), when going from seated to standing compared to controls. Findings suggest adults with PPCS have altered autonomic function relative to controls. Physical activity level and deconditioning are potential treatment targets to improve autonomic function.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 11","pages":"e70378"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuli Sakko, Mikko P Tulppo, Peppi Koivunen, Joona Tapio
{"title":"Higher hemoglobin levels are associated with adverse heart rate variability in a middle-aged birth cohort.","authors":"Samuli Sakko, Mikko P Tulppo, Peppi Koivunen, Joona Tapio","doi":"10.14814/phy2.70406","DOIUrl":"10.14814/phy2.70406","url":null,"abstract":"<p><p>High hemoglobin (Hb) levels within normal variation range are considered beneficial. However, lower Hb levels within normal variation range are associated with healthier cardiovascular traits. Heart rate variability (HRV) and baroreflex sensitivity (BRS) are dysregulated in cardiovascular diseases (CVDs). We have shown in a hypertensive cohort that higher Hb levels are associated with impaired HRV and BRS. As CVDs are exacerbated by aging, conditions like hypertension and factors such as smoking, further studies on the association of Hb levels and HRV and BRS on younger and healthier populations are required for the generalization of these associations. The aims were to cross-sectionally study the association of Hb levels with HRV and BRS in the Northern Finland Birth Cohort 1966 (NFBC1966) at 46 years (n = 5342) and to evaluate confounding factors, such as smoking, on these associations. Higher Hb levels within normal variation range were associated with adverse time-domain measures, including elevated heart rate (HR). Hb levels were negatively associated with high-frequency (HF) power and positively with the low frequency (LF) to HF ratio (LF/HF). These associations were influenced by sex, metabolic parameters, and smoking but were observed regardless of these factors. For BRS, adjusting for metabolic covariates nullified the association with Hb levels.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 11","pages":"e70406"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saeed Niazmand, S A Rahim Rezaee, Jamshid Gholizadeh Navashenaq, Nema Mohamadian Roshan, Mohsen Ghoryani, Houshang Rafatpanah, Maryam Mahmoudabady, Yousef Baghcheghi, Maryam Paseban, Mahdiyeh Hedayati-Moghadam
{"title":"HTLV-1 infection altered expression of CCR2, CXCR2, eNOS genes, and oxidative stress in aorta and heart of male mice.","authors":"Saeed Niazmand, S A Rahim Rezaee, Jamshid Gholizadeh Navashenaq, Nema Mohamadian Roshan, Mohsen Ghoryani, Houshang Rafatpanah, Maryam Mahmoudabady, Yousef Baghcheghi, Maryam Paseban, Mahdiyeh Hedayati-Moghadam","doi":"10.14814/phy2.70409","DOIUrl":"10.14814/phy2.70409","url":null,"abstract":"<p><p>Viral infections are associated with the disruption of oxidative stress and the progression of inflammatory mechanisms that play pivotal roles in cardiovascular diseases. In the present study, several inflammatory and oxidative stress markers were examined in HTLV-1-infected male BALB/c mice. Twenty BALB/c mice were divided into two groups: the HTLV-1-infected group and the control group. Two months later, samples were collected from blood, aorta, heart, spleen, and lymph nodes. Finally, the levels of various plasma markers (lipid profile, creatine phosphokinase, nitric oxide, GSH, and total thiol), oxidative stress markers (SOD and CAT activity, MDA and total thiol levels), chemokine receptors genes expression (CCR2, CXCR2, CCR1) and eNOS expression in aortic and heart tissues, as well as histopathological changes in the heart, were evaluated. Plasma triglyceride, creatine phosphokinase, nitric oxide, and aorta malondialdehyde levels in the HTLV-1-infected group were higher than those in the control group. In contrast, total thiol levels in plasma, heart, and aorta, plasma glutathione levels, and the activities of superoxide dismutase and catalase were lower compared to the control group. The expression of CCR2 and CXCR2 was elevated in the aorta of the HTLV-1-infected group, while eNOS expression was reduced in both aortic and heart tissues. HTLV-1 may contribute to inflammatory responses and oxidative stress in cardiovascular tissues.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 11","pages":"e70409"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
André C Silveira, Júlio S Hasegawa, Ramon Cruz, Monique Matsuda, Mônica V Marquezini, Adriano Eduardo Lima-Silva, Paulo Saldiva, Michael S Koehle, Rômulo Bertuzzi
{"title":"Does traffic-related air pollution exposure alter blood gas parameters in recreationally trained male cyclists during prolonged endurance exercise?","authors":"André C Silveira, Júlio S Hasegawa, Ramon Cruz, Monique Matsuda, Mônica V Marquezini, Adriano Eduardo Lima-Silva, Paulo Saldiva, Michael S Koehle, Rômulo Bertuzzi","doi":"10.14814/phy2.70408","DOIUrl":"10.14814/phy2.70408","url":null,"abstract":"<p><p>Exposure to air pollution has been a significant challenge in large cities as São Paulo, Brazil, particularly for individuals exercising outdoors. The increasing on ventilation (VE) during physical effort can lead to greater pollutant inhalation. Our goal in the present study evaluated whether air pollution exposure affects venous blood gases and if it has an impact on performance during a 50-km cycling time trial (TT). Ten male cyclists performed the TT in an environmental chamber under TRAP and filtered air conditions. Venous blood samples collected pre- and post-TT were analyzed for pH, PvCO<sub>2</sub> (partial pressure of carbon dioxide in venous blood), PvO<sub>2</sub> (partial pressure of oxygen in venous blood) hematocrit (Htc), hemoglobin (Hb), and oxygen saturation (SvO<sub>2</sub>). PM<sub>2.5</sub> levels were significantly lower in filtered air (11.2 ± 4.7 μm/m<sup>3</sup>) than in TRAP (34.6 ± 10.8 μm/m<sup>3</sup>). There was no significant difference in mean power output between conditions (p = 0.907, d = 0.038). Blood gas parameters showed no condition effect or interaction, but time significantly affected PvO<sub>2</sub> (p = 0.04), Hb (p < 0.01), Htc (p < 0.01), and PvCO<sub>2</sub> (p = 0.02). These findings suggest recreationally trained cyclists experience no performance impairment under TRAP, with minimal changes in venous blood gas parameters.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 11","pages":"e70408"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina Karamanova, Kaleb T Morrow, Alana Maerivoet, Jillian Madine, Ming Li, Raymond Q Migrino
{"title":"Medin induces pro-inflammatory activation of human brain vascular smooth muscle cells.","authors":"Nina Karamanova, Kaleb T Morrow, Alana Maerivoet, Jillian Madine, Ming Li, Raymond Q Migrino","doi":"10.14814/phy2.70418","DOIUrl":"10.14814/phy2.70418","url":null,"abstract":"<p><p>Medin, a common amyloidogenic protein, accumulates in the vasculature with aging. We evaluated the effects of medin on human brain vascular smooth muscle cell (VSMC) activation. VSMCs were exposed to medin (0.5, 1, and 5 μM) without or with the small molecule nuclear factor-κB (NFκB) inhibitor RO106-9920 (10 μM). Polymerase chain reaction, Western blot/enzyme-linked immunosorbent assays were used to quantify gene and protein expressions/secretions, respectively, of pro-inflammatory factors (interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1) and structural and enzyme proteins associated with VSMC phenotypic transformation (smooth muscle actin alpha 2 (ACTA2), myosin heavy chain 11 (MYH11) and NADPH oxidase 4 (NOX4)). Medin increased VSMC gene expression and protein secretion of IL-6, IL-8, and MCP-1 (protein secretion 46.0 ± 12.8x, 20.2 ± 4.1x, and 8.7 ± 3.1x, respectively, medin 5 μM versus vehicle, p < 0.05). There was no change in gene/protein expressions of ACTA2, MYH11, and NOX4. Co-treatment with RO106-9920 reduced medin-induced increases in IL-6 and IL-8 with a trend towards reduced MCP-1 secretion. Medin induced pro-inflammatory activation of human brain VSMCs that is mediated in part by NFκB. Acute medin treatment did not alter structural proteins involved in VSMC phenotypic transformation. The findings support medin as a potential novel mediator of and therapeutic target for vascular aging pathology.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 11","pages":"e70418"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beneficial effects of magnesium nitrate on disease severity in male rats with monocrotaline-induced pulmonary hypertension.","authors":"Masashi Tawa, Shunto Abe, Ako Fujita, Riku Ando, Hajime Yoshinari, Keisuke Nakagawa, Mamoru Ohkita","doi":"10.14814/phy2.70416","DOIUrl":"https://doi.org/10.14814/phy2.70416","url":null,"abstract":"<p><p>Inorganic nitrates and magnesium salts are effective in the treatment of pulmonary hypertension (PH). Here, we examined whether magnesium nitrate, which belongs to both categories, has a vasorelaxant effect on pulmonary arteries and protects against PH. In organ chamber experiments with isolated rat pulmonary arteries, high concentrations of magnesium nitrate (3 and 10 mM) produced weak relaxation, and phenylephrine-induced contraction was attenuated in the presence of 3 mM magnesium nitrate. Exposure to magnesium nitrate (3 mM) did not affect acetylcholine-induced relaxation. In rats with monocrotaline (MCT)-induced PH, supplementation of drinking water with magnesium nitrate (3 and 10 mM) for 2 weeks from 2 weeks after MCT injection (60 mg/kg, s.c.) alleviated right ventricular systolic pressure elevation, regardless of the dose. High-dose magnesium nitrate also suppressed pulmonary arterial medial thickening. Treatment with magnesium nitrate did not reduce right ventricular hypertrophy. Low-dose magnesium nitrate tended to increase plasma nitrate levels, which increased significantly at a higher dose. High-dose magnesium nitrate also increased plasma magnesium levels. These findings suggest that magnesium nitrate has antispasmodic effects on pulmonary arteries and is effective in halting the progression of PH, demonstrating its usefulness in managing PH.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 12","pages":"e70416"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marissa I McGilvrey, Bethany Fortier, Diana Cooke, Maryam A Mahdi, Benjamin Tero, Christian M Potts, Abigail Kaija, Larisa Ryzhova, Carolina Cora, Adam Richardson, Douglas Guzior, Ilka Pinz, Calvin Vary, Robert A Koza, Gene Ables, Lucy Liaw
{"title":"Short-term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice.","authors":"Marissa I McGilvrey, Bethany Fortier, Diana Cooke, Maryam A Mahdi, Benjamin Tero, Christian M Potts, Abigail Kaija, Larisa Ryzhova, Carolina Cora, Adam Richardson, Douglas Guzior, Ilka Pinz, Calvin Vary, Robert A Koza, Gene Ables, Lucy Liaw","doi":"10.14814/phy2.70405","DOIUrl":"https://doi.org/10.14814/phy2.70405","url":null,"abstract":"<p><p>Dietary methionine restriction (MetR) promotes metabolic health, and we tested the impact of short durations of MetR on high fat diet (HFD)-induced metabolic dysfunction with the maintenance of HFD. Male C57BL/6J mice were fed HFD from 10 to 25 weeks of age, then maintained on HFD or fed HFD with 80% reduced methionine (HFD-MetR) for 3, 5, or 10 days. Blood, liver, adipose tissue, and aortae underwent phenotypic assessment, proteomics, and metabolomics. HFD-MetR induced rapid weight loss and robust metabolic improvement within 10 days. Significant reductions in body weight, circulating triglycerides, glucose, insulin, adipokines and hepatokines reflected metabolic health. Proteomics revealed enriched metabolic signatures in perivascular adipose tissue (PVAT) and structural remodeling signatures in aorta. Metabolomics identified a cardioprotective signature in blood plasma, and activated mitochondrial activity and energy production in liver and brown adipose tissue. HFD-MetR reversed metabolic dysfunction, and novel proteomic and metabolomic signatures were identified. Multi-organ molecular changes in lipid metabolism, mitochondrial function, and bioenergetics are predicted to impact adipose tissue and liver function and cardiovascular health. Our identification of rapid changes in protein and metabolite signatures with accelerated restoration of metabolic health can be leveraged to evaluate biomarkers of metabolic health and disease in a translational context.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 12","pages":"e70405"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}