American journal of physiology. Endocrinology and metabolism最新文献

{"title":"A new C-peptide minimal model to assess β-cell responsiveness to glucagon in individuals with and without type 2 diabetes.","authors":"Federica Boscolo, Edoardo Faggionato, Andrew A Welch, Rahele A Farahani, Aoife M Egan, Adrian Vella, Chiara Dalla Man","doi":"10.1152/ajpendo.00424.2024","DOIUrl":"10.1152/ajpendo.00424.2024","url":null,"abstract":"<p><p>Glucagon regulates its own secretion indirectly by stimulating β-cells to secrete insulin. This may serve as a compensatory mechanism to enhance β-cell function in individuals with, or predisposed to, type 2 diabetes (T2D). However, tools to quantify glucagon-induced C-peptide secretion rate (SR) are lacking. To bridge this gap, we developed a novel model-based method to provide quantitative indices of β-cell function in response to a glucagon bolus in individuals without and with type 2 diabetes. Eight individuals without diabetes [3 M, age = 55 ± 9 yr, body mass index (BMI) = 32 ± 4 kg/m²] and six with T2D (1 M, age = 59 ± 5 yr, BMI = 35 ± 6 kg/m²) underwent a 210-min hyperglycemic clamp (∼9 mmol/L). After 180 min, a 1 mg bolus of glucagon was administered over 1 min, and plasma glucagon and C-peptide concentrations were frequently measured over 30 min. We tested a battery of mathematical models and selected the best one based on standard criteria. The optimal model assumes that C-peptide SR is made up of two components, one proportional to the above basal glucagon, through parameter Γ_s (static), and one proportional to glucagon rate of change, through parameter Γ_d (dynamic responsivity to the hormone). An index of total β-cell responsivity to glucagon, Γ, was also derived from Γ_s and Γ_d. The model estimated Γ_s and Γ were significantly higher in individuals without diabetes compared with T2D (<i>P</i> < 0.05), whereas Γ_d was not. Our findings reveal notable differences in both static and total insulin secretory response to glucagon in people with diabetes as compared with those without diabetes.<b>NEW & NOTEWORTHY</b> In this study, we propose a new mathematical model able to quantify C-peptide secretion and β-cell responsivity in response to a glucagon bolus in individuals without and with type 2 diabetes. We show that individuals with type 2 diabetes exhibit reduced β-cell responsivity to glucagon.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E470-E477"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381501","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":"Possible brain regions involved in parturition in mice.","authors":"Xia Wang, Yueling Zang, Yunhe Ma, Jun Li, Xing Li, Qiping Li, Xiang Liao, Xiaowei Chen, Jian Han, Xiaoling Zhao, Han Qin, Tingliang Jian","doi":"10.1152/ajpendo.00430.2024","DOIUrl":"10.1152/ajpendo.00430.2024","url":null,"abstract":"<p><p>Parturition is a vital physiological process in the reproduction of female mammals, regulated by neurohumoral mechanisms coordinated by the central nervous system. The uterus is essential for this process; however, the neural pathways connecting the brain to the uterus remain poorly understood. In this study, we combined the pseudorabies virus (PRV) tracing tool with c-Fos immunofluorescence staining to identify brain regions that may regulate uterine muscle activity during parturition. We observed that the paraventricular nucleus (PVN), periaqueductal gray (PAG), and locus coeruleus (LC) were colabeled with PRV and c-Fos. Subsequently, we focused on the PVN to determine whether its activity correlated with parturition behavior. We used fiber photometry to record Ca²⁺ activity in the PVN during parturition in freely behaving mice and found a strong correlation between PVN activity and parturition behavior. Our results demonstrate that this method is both accessible and reliable for studying the roles of central-peripheral neural pathways involved in parturition behavior and suggest that PVN may be a key brain node for parturition.<b>NEW & NOTEWORTHY</b> Parturition is a vital physiological process in the reproduction of female mammals. Here, the authors established a method that combined retrograde tracing, c-Fos immunofluorescence staining, and fiber photometry to study the roles of central-peripheral neural pathways involved in parturition. Our method is simple and reliable to investigate the roles of central-peripheral neural pathways involved in a range of physiological processes in freely moving animals.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E325-E336"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998534","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":"Long-lasting recombinant HEXA treatment improves hepatic steatosis and glycemic control in mild, but not severe, metabolic dysfunction-associated steatohepatitis.","authors":"Sihan Lin, Li Dong, William De Nardo, Michael G Leeming, Zhili Cheng, Nicholas A Williamson, Matthew J Watt, Magdalene K Montgomery","doi":"10.1152/ajpendo.00359.2024","DOIUrl":"10.1152/ajpendo.00359.2024","url":null,"abstract":"<p><p>The prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing at an alarming rate. To date, only one therapy has been provisionally approved for the treatment of MASH and liver fibrosis, and novel strategies are urgently needed. In addition, the frequent coexistence of MASH and type 2 diabetes has further intensified interest in devising comprehensive therapies to simultaneously tackle both diseases. We have recently shown that increasing hepatic and/or circulating levels of hexosaminidase A (HEXA), a lysosomal enzyme that remodels GM2 to GM3 gangliosides within lipid rafts, offers therapeutic benefits for metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Taking advantage of the MUP-uPA mouse model of MASH, including both wild-type (WT) mice with mild MASH and MUP-uPA mice with severe MASH and fibrosis, we show that biweekly treatment with a long-lasting HEXA-FC analog improves features of MASLD, including hepatic steatosis and hepatocyte ballooning, in mice with mild MASH, as well as glycemic control across both mouse models. Mechanistically, HEXA-FC enhances hepatic fatty acid oxidation and peripheral glucose disposal while not impacting endogenous glucose production. Together, these outcomes suggest that while HEXA-FC treatment may offer therapeutic benefits in mild MASH and insulin resistance, it is ineffective against severe MASH and liver fibrosis.<b>NEW & NOTEWORTHY</b> The prevalence of metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes is increasing. Here, we show that chronic FC-HEXA recombinant protein treatment reduces hepatic lipid accumulation and improves blood glucose control in mice with mild MASH and insulin resistance.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E377-E394"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381505","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":"Proteomic profiling reveals alterations in metabolic and cellular pathways in severe obesity and following metabolic bariatric surgery.","authors":"Prince Dadson, Miikka-Juhani Honka, Tomi Suomi, P A Nidhina Haridas, Anne Rokka, Senthil Palani, Elena Goltseva, Ning Wang, Anne Roivainen, Paulina Salminen, Peter James, Vesa M Olkkonen, Laura L Elo, Pirjo Nuutila","doi":"10.1152/ajpendo.00220.2024","DOIUrl":"10.1152/ajpendo.00220.2024","url":null,"abstract":"<p><p>In this study, we investigated the impact of bariatric surgery on the adipose proteome to better understand the metabolic and cellular mechanisms underlying weight loss following the procedure. A total of 46 patients with severe obesity were included, with samples collected both before and after bariatric surgery. In addition, 15 healthy individuals without obesity who did not undergo surgery served as controls and were studied once. We utilized quantitative liquid chromatography-tandem mass spectrometry analysis to conduct a large-scale proteomic study on abdominal subcutaneous biopsies obtained from the study participants. Our proteomic profiling revealed that among the 2,254 compared proteins, 46 were upregulated and 34 were downregulated 6 months post surgery compared with baseline [false discovery rate (FDR) < 0.01]. We observed a downregulation of proteins associated with mitochondrial integrity, amino acid catabolism, and lipid metabolism in the patients with severe obesity compared with the controls. Bariatric surgery was associated with an upregulation in pathways related to mitochondrial function, protein synthesis, folding and trafficking, actin cytoskeleton regulation, and DNA binding and repair. These findings emphasize the significant changes in metabolic and cellular pathways following bariatric surgery, highlighting the potential mechanisms underlying the observed health improvements postbariatric surgery. The data provided alongside this paper will serve as a valuable resource for the development of targeted therapeutic strategies for obesity and related metabolic complications. ClinicalTrials.gov registration numbers: NCT00793143 (registered on 19 November 2008) (https://clinicaltrials.gov/ct2/show/NCT00793143) and NCT01373892 (registered on 15 June 2011) (https://clinicaltrials.gov/ct2/show/NCT01373892).<b>NEW & NOTEWORTHY</b> Our study investigates the effects of metabolic bariatric surgery on adipose tissue proteins, highlighting the mechanisms driving weight loss postsurgery. Through extensive proteomic analysis of adipose biopsies from patients with severe obesity pre- and postsurgery, alongside healthy subjects without obesity, we identified significant alterations in metabolic pathways. These findings provide insights into potential therapeutic targets for obesity-related complications.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E311-E324"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998544","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":"Hunger games: a role for cAMP.","authors":"Jane Jose Vattathara, Carlos Diéguez, Miguel López","doi":"10.1152/ajpendo.00524.2024","DOIUrl":"10.1152/ajpendo.00524.2024","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E287-E288"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021620","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":"Postexercise myofibrillar protein synthesis rates do not differ following 1.5 g essential amino acids compared with 15 and 20 g of whey protein in young females.","authors":"Marianna C A Apicella, Tom S O Jameson, Alistair J Monteyne, George F Pavis, Doaa R Abdelrahman, Andrew J Murton, Nima Alamdari, Marlou L Dirks, Benjamin T Wall, Francis B Stephens","doi":"10.1152/ajpendo.00365.2024","DOIUrl":"10.1152/ajpendo.00365.2024","url":null,"abstract":"<p><p>Optimal adaptation to resistance exercise requires maximal rates of myofibrillar protein synthesis (MyoPS), which can be achieved by postexercise consumption of >20 g of protein or ∼2 g of the essential amino acid (EAA) leucine. These nutritional recommendations are based on studies in males. The aim of the present study was to compare the postexercise MyoPS response to nutrition in young females. Twenty-eight healthy, females [age: 28 ± 8 yr; body mass index (BMI): 24 ± 3 kg/m²] received a primed-continuous infusion of l-[<i>ring</i>-²H₅]-phenylalanine and completed a bout of unilateral resistance exercise before ingesting a drink containing either 1.5 g EAA (<i>n</i> = 10), 15 g (<i>n</i> = 10), or 20 g (<i>n</i> = 8) whey protein, containing 0.6, 1.5, and 2.0 g leucine, respectively. Blood and muscle samples were collected pre- and postexercise and drink ingestion to assess MyoPS and gene expression. Drink ingestion increased plasma leucine concentrations following 15 and 20 g whey protein compared with 1.5 g EAA (<i>P</i> < 0.0001). Exercise and drink ingestion increased basal (0.060 ± 0.026, 0.063 ± 0.034, 0.051 ± 0.023%·h^-1) MyoPS rates between 0 and 2 h to 0.117 ± 0.028, 0.098 ± 0.051 and 0.116 ± 0.034%·h^-1 (<i>P</i> < 0.0001) and between 2 and 4 h to 0.110 ± 0.028, 0.074 ± 0.038, and 0.082 ± 0.061%·h^-1 (<i>P</i> = 0.008) for 1.5, 15, and 20 g drinks, respectively, with no differences observed between drinks (<i>P</i> = 0.416). The postexercise changes in muscle mRNA expression of genes involved in protein turnover, substrate utilization, remodeling, and inflammation did not differ between drinks (<i>P</i> > 0.050). Postexercise MyoPS did not differ following ingestion of 1.5, 15, and 20 g drinks, hence 0.6 g leucine may be sufficient to stimulate postexercise MyoPS in young females.<b>NEW & NOTEWORTHY</b> This study provides evidence that postexercise myofibrillar protein synthesis rates do not differ following the ingestion of 1.5 g of essential amino acids, 15 and 20 g of whey protein, containing 0.6, 1.5, and 2.0 g of leucine, respectively, in young females. Protein and leucine doses below current recommendations, >20 g of protein or ∼2 g leucine, may be sufficient to optimally stimulate myofibrillar protein synthesis in young females.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E420-E434"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063096","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":"Counterregulatory responses of healthy cats to insulin- induced-hypoglycemia.","authors":"Jocelyn Mott, Christopher Adin, Chiquitha Crews, Marc Evan Salute, Antonio Maria Tardo, Lauren Porter, Alisa Berg, Chen Gilor","doi":"10.1152/ajpendo.00269.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00269.2024","url":null,"abstract":"<p><p>In health, insulin-induced-hypoglycemia (IIH) activates counterregulatory hormones responses and parasympathetic (PS) and sympathoadrenal systems which leads to increased glucagon secretion. In diabetes mellitus, these responses are impaired, resulting in greater severity and delayed recovery from hypoglycemia. These counterregulatory responses in health and disease have been documented in humans, rodents, and dogs, but not yet in cats. The aim of this study was to describe and quantify glucagon, PS and cortisol responses in healthy purpose bred cats at increasing levels of IIH. Glucagon, cortisol, and pancreatic polypeptide (PP) were measured at euglycemia and during stepped hyperinsulinemic-hypoglycemic clamps at two levels of glycemia: moderate hypoglycemia (blood glucose [BG] ~60 mg/dL) and severe hypoglycemia (BG ~45 mg/dL). At moderate hypoglycemia, a cortisol response occurred. At moderate hypoglycemia there was no change in PP and glucagon from baseline. With severe hypoglycemia, both glucagon and PP concentrations decreased from baseline and were not supportive of glucagon and parasympathetic activation in response to IIH. While cortisol increases during IIH, the counterregulatory response to IIH in healthy cats differs from other species, in that glucagon and PS responses were not detected. Moreover, in face of constant inhibition by IIH, glucagon secretion seems dependent on glucose, decreasing when glucose infusion rates were decreased. Understanding counterregulatory responses to hypoglycemia in healthy cats is the first step to exploring how diabetes might impair these responses in cats, as seen in other species.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514394","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":"Carbohydrate supplementation maintains physical performance during short-term energy deficit despite reductions in exogenous glucose oxidation.","authors":"Lee M Margolis, Jillian T Allen, Nancy E Murphy, Christopher T Carrigan, Emily E Howard, David E Barney, Devin J Drummer, Julia Michalak, Arny A Ferrando, Stefan M Pasiakos, Jess A Gwin","doi":"10.1152/ajpendo.00418.2024","DOIUrl":"10.1152/ajpendo.00418.2024","url":null,"abstract":"<p><p>Exogenous glucose oxidation is reduced 55% during aerobic exercise after 3 days of complete starvation. Whether energy deficits more commonly experienced by athletes and military personnel similarly affect exogenous glucose oxidation and what impact this has on physical performance remains undetermined. This randomized, longitudinal parallel study aimed to assess the effects of varying magnitudes of energy deficit (DEF) on exogenous glucose oxidation and physical performance compared with energy balance (BAL). Participants consumed a 4-day BAL diet, followed by a 6-day 20% (<i>n</i> = 10), 40% (<i>n</i> = 10), or 60% (<i>n</i> = 10) DEF diet. At the end of each energy phase, participants performed 90-min of steady-state cycle ergometry (56 ± 3% V̇o_2peak) while consuming a glucose drink (80 g), followed by a time to exhaustion (TTE) performance test. Substrate oxidation (g/min) was determined by indirect calorimetry and ¹³C-glucose. Muscle glycogen (mmol/kg dry wt) and transcript accumulation were assessed in rested fasted muscle collected before exercise in each phase. Muscle glycogen was lower (<i>P</i> = 0.002) during DEF (365 ± 179) than BAL (456 ± 125), regardless of group. Transcriptional regulation of glucose uptake (<i>GLUT4</i> and <i>IRS2</i>) and glycogenolysis (<i>HKII</i> and <i>PKM</i>) were lower (<i>P</i> < 0.05) during DEF than BAL, independent of group. Regardless of group, exogenous glucose oxidation was 10% lower (<i>P</i> < 0.001) during DEF (0.38 ± 0.08) than BAL (0.42 ± 0.08). There was no evidence of a difference in TTE between BAL and DEF or between groups. In conclusion, despite modest reduction in exogenous glucose oxidative capacity during energy deficit, physical performance was similar compared with balance.<b>NEW & NOTEWORTHY</b> Short-term (6-day) energy deficit reduced exogenous glucose oxidation during exercise. Though less exogenous glucose was used for fuel, young healthy individuals appear to have a metabolic resilience to short-term periods of low energy availability, with no observed differences in the ability to take up and oxidize exogenous glucose between minimal (20%), moderate (40%), and severe (60%) energy deficits. Similar metabolic responses to carbohydrate supplementation independent of deficit severity likely contributed to sustainment of physical performance.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E242-E253"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998516","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":"L-type calcium channel blockade worsens glucose tolerance and β-cell function in C57BL6/J mice exposed to intermittent hypoxia.","authors":"Stanley M Chen Cardenas, Tess A Baker, Larissa A Shimoda, Ernesto Bernal-Mizrachi, Naresh M Punjabi","doi":"10.1152/ajpendo.00423.2023","DOIUrl":"10.1152/ajpendo.00423.2023","url":null,"abstract":"<p><p>Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for the treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated. Adult male C57BL6/J mice were exposed to either nifedipine or vehicle concurrently with IH or intermittent air (IA) over 5 days. IH exposure entailed cycling fractional-inspired oxygen levels between 0.21 and 0.055 at a rate of 60 events/h. Nifedipine (20 mg/kg/day) or vehicle was administered via subcutaneous osmotic pumps resulting in four groups of mice: IA-vehicle (control), IA-nifedipine, IH-vehicle, and IH-nifedipine. Compared with IA (control), IH increased fasting glucose (mean Δ: 33.0 mg/dL; <i>P</i> < 0.001) and insulin (mean Δ: 0.53 ng/mL; <i>P</i> < 0.001) with nifedipine having no independent effect. Furthermore, glucose tolerance was worse with nifedipine alone, and IH further exacerbated the impairment in glucose disposal (<i>P</i> = 0.013 for interaction). Nifedipine also decreased glucose-stimulated insulin secretion and the insulinogenic index, with addition of IH attenuating those measures further. There were no discernible alterations in insulin biosynthesis/processing, insulin content, or islet morphology. These findings underscore the detrimental impact of IH on insulin sensitivity and glucose tolerance while highlighting that nifedipine exacerbates these disturbances through impaired β-cell function. Consequently, cautious use of L-type calcium channel blockers is warranted in patients with OSA, particularly in those at risk for type 2 diabetes.<b>NEW & NOTEWORTHY</b> The results of this study demonstrate the interaction between intermittent hypoxemia (IH) and nifedipine in a murine model. IH raises fasting glucose and insulin levels, with nifedipine exacerbating these disturbances. Glucose tolerance worsens when nifedipine is administered alone, and IH magnifies the impairment in glucose disposal. These findings raise the possibility of potential deleterious effects of L-type calcium channel blockers in patients with obstructive sleep apnea (OSA).</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"328 2","pages":"E161-E172"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021717","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":"Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity.","authors":"Yem J Alharithi, Elysse A Phillips, Tim D Wilson, Sneha P Couvillion, Carrie D Nicora, Priscila Darakjian, Shauna Rakshe, Suzanne S Fei, Brittany R Counts, Thomas O Metz, Robert P Searles, Sushil Kumar, Alina Maloyan","doi":"10.1152/ajpendo.00333.2024","DOIUrl":"10.1152/ajpendo.00333.2024","url":null,"abstract":"<p><p>Maternal obesity puts the offspring at high risk of developing obesity and cardiometabolic diseases in adulthood. Here, we utilized a mouse model of maternal high-fat diet (HFD)-induced obesity that recapitulates metabolic perturbations seen in humans. We show increased adiposity in the offspring of HFD-fed mothers (Off-HFD) when compared with the offspring of regular diet-fed mothers (Off-RD). We have previously reported significant immune perturbations in the bone marrow of newly weaned Off-HFD. Here, we hypothesized that lipid metabolism is altered in the bone marrow of Off-HFD versus Off-RD. To test this hypothesis, we investigated the lipidomic profile of bone marrow cells collected from 3-week-old Off-RD and Off-HFD. Diacylglycerols (DAGs), triacylglycerols (TAGs), sphingolipids, and phospholipids were remarkably different between the groups, independent of fetal sex. Levels of cholesteryl esters were significantly decreased in Off-HFD, suggesting reduced delivery of cholesterol. These were accompanied by age-dependent progression of mitochondrial dysfunction in bone marrow cells. We subsequently isolated CD11b+ myeloid cells from 3-wk-old mice and conducted metabolomic, lipidomic, and transcriptomic analyses. The lipidomic profiles of myeloid cells were similar to those of bone marrow cells and included increases in DAGs and decreased TAGs. Transcriptomics revealed altered expression of genes related to immune pathways, including macrophage alternative activation, B-cell receptors, and transforming growth factor-β signaling. All told, this study revealed lipidomic, metabolomic, and gene expression abnormalities in bone marrow cells broadly, and in bone marrow myeloid cells particularly, in the newly weaned offspring of mothers with obesity, which might at least partially explain the progression of metabolic and cardiovascular diseases in their adulthood.<b>NEW & NOTEWORTHY</b> Our data revealed significant immunometabolic perturbations in the bone marrow and myeloid cells in the newly weaned offspring born to mothers with obesity. Adaptation to an adverse maternal intrauterine environment affects bone marrow metabolism at a very young age and might affect responses to immune challenges that appear later in life, for example, infections or cancer.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E254-E271"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942696","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}