American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Hypothalamus and brainstem circuits in the regulation of glucose homeostasis.","authors":"Zitian Lin, Yunxin Xuan, Yingshi Zhang, Qirui Zhou, Weiwei Qiu","doi":"10.1152/ajpendo.00474.2024","DOIUrl":"10.1152/ajpendo.00474.2024","url":null,"abstract":"<p><p>The central nervous system (CNS) senses and integrates blood glucose status, regulating its levels through communication with peripheral organs. Since traditional wisdom holds that the hypothalamus primarily controls glucose homeostasis, the brainstem, although less studied, has been emerging as a key player in blood glucose metabolism. Although the brainstem is reciprocally wired with the hypothalamus, their interactions are crucial for glucose control. Here, we focus on classic discoveries and recent advancements of hypothalamic and brainstem nodes that regulate glucose homeostasis. Based on the current progress and development for central regulation of blood sugar, we propose that the circuitry and cellular mechanisms for how hypothalamus and brainstem coordinate in blood sugar regulation are crucial; hence, a deeper understanding of both nuclei could shed light on a future cure for diabetes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E588-E598"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565781","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":"Six-hour hypoxia-induced protein degradation in M. gastrocnemius of 24-day-old mice by activating FOXO1 and suppressing AKT-mTORC1.","authors":"Jingyi Song, Marcel Jaklofsky, Claudia Carmone, Vincent de Boer, Niels Wever, Jaap Keijer, Sander Grefte","doi":"10.1152/ajpendo.00508.2024","DOIUrl":"10.1152/ajpendo.00508.2024","url":null,"abstract":"<p><p>Long-term hypoxia has been associated with skeletal muscle atrophy, including increased protein degradation over protein synthesis. This contrasts sharply with muscle hypertrophy and net protein synthesis occurring in the developing skeletal muscle of young mice. Here, we aimed to understand the impact of acute, physiologically plausible environmental hypoxia on muscle proteostasis of the M. gastrocnemius of young mice. Fasted prepubertal, 24-day-old male B6JRccHsd(B6J)-<i>Nnt⁺</i>/Wuhap mice with similar body weight and lean mass were exposed to normobaric hypoxia (12% O₂) or normoxia (20.9% O₂) for 6 h. The transcriptome (<i>n</i> = 12) and protein (<i>n</i> = 6) responses of the M. gastrocnemius were analyzed. A hypoxic response of M. gastrocnemius was confirmed by increased expression of hypoxia-inducible factor 1 (HIF1) (<i>Ankrd37</i> and <i>Ddit4</i>) and forkhead box-O (FOXO) 1 (<i>Depp1</i> and <i>Ddit4</i>) target genes. RNA-Seq analysis revealed that hypoxia activated FOXO signaling, which was confirmed by increased FOXO1 protein levels and decreased p-AKT/AKT ratio. Detailed mapping of the FOXO1 pathway suggests a strong FOXO1-mediated hypoxic effect on protein degradation and synthesis. A central role of <i>Atf4</i> is suggested by the hypoxic-dependent positive correlations with FOXO1, FBXO32, <i>Depp1</i>, <i>Eif4ebp1</i>, and <i>Ddit4</i>. Further analyses showed increased FBXO32, which positively correlated with FOXO1, and decreased p-S6K/S6K and p-4E-BP1/4E-BP1 ratios. Our results showed for the first time that a 6-h exposure to 12% O₂ normobaric hypoxia in 24-day-old mice activates FOXO1 signaling in M. gastrocnemius, resulting in decreased protein synthesis and increased protein degradation most likely via reduced energy availability, which may be relevant for infant air or high altitude traveling.<b>NEW & NOTEWORTHY</b> We newly investigated an acute (6 h) hypoxic exposure (12% O₂) in developing and growing M. gastrocnemius of 24-day-old mice. This acute hypoxia significantly enhanced muscle protein breakdown via the activation of FOXO1 and subsequently FBXO32, whereas also suppressing protein synthesis via the reduced p-S6K/S6K and p-4E-BP1/4E-BP1 and thus AKT-mTORC1 pathway. Together these changes observed could potentially hamper the muscle development of young mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E620-E632"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646953","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":"Central FGF19 signaling enhances energy homeostasis and adipose tissue thermogenesis through sympathetic activation in obese mice.","authors":"Lucas Zangerolamo, Marina Carvalho, Carina Solon, Davi Sidarta-Oliveira, Gabriela M Soares, Carine Marmentini, Antonio C Boschero, Yu-Hua Tseng, Licio A Velloso, Helena C L Barbosa","doi":"10.1152/ajpendo.00488.2024","DOIUrl":"10.1152/ajpendo.00488.2024","url":null,"abstract":"<p><p>Fibroblast growth factor 19 (FGF19) signaling in the brain is associated with body weight loss, reduced food intake, and improved glycemic control in obese mice through unclear mechanisms. Here, we investigated the effects of central FGF19 administration on peripheral tissues, focusing on adipose tissue and its contributions to body weight loss. Using single-cell RNA sequencing of the adult murine hypothalamus, we found that FGF19 has the potential to target multiple cell populations, including astrocytes-tanycytes, microglia, neurons, and oligodendrocytes. Central delivery of FGF19 decreased body weight gain and ameliorated glucose-insulin homeostasis in diet-induced obese (DIO) mice. These results were accompanied by increased energy expenditure and reduced peripheric inflammation. Notably, these effects were attributable to the increased activity of thermogenic adipocytes, as upregulated thermogenic markers in brown and inguinal adipose tissue and improved cold tolerance were induced by central FGF19. However, under blunted sympathetic activity, the described effects were abolished. Moreover, cold exposure induced upregulation of FGF19 receptors and coreceptors specifically in the hypothalamus, suggesting a critical metabolic adaptation for thermoregulation and energy homeostasis. Our findings indicate that central FGF19 signaling improves energy homeostasis in DIO mice, at least in part, by stimulating sympathetic activity and adipose tissue thermogenesis. These findings highlight FGF19's potential as a therapeutic target for obesity and metabolic disorders.<b>NEW & NOTEWORTHY</b> Although most studies associate central fibroblast growth factor 19 (FGF19) with reduced food intake, our findings highlight its role in enhancing thermogenesis in white and brown adipose tissues through sympathetic activation. Central FGF19 not only regulates feeding but also drives peripheral adaptations critical for energy homeostasis and body weight control under obesogenic conditions. These insights underscore the significance of top-down mechanisms in FGF19 action and its therapeutic potential for combating obesity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E524-E542"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584348","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":"Vertical sleeve gastrectomy and semaglutide have distinct effects on skeletal health and heart function in obese male mice.","authors":"Caroline de Carvalho Picoli, Sergey Tsibulnikov, Mavy Ho, Victoria DeMambro, Tiange Feng, May Eltahir, Phuong T Le, Carolyn Chlebek, Clifford J Rosen, Sergey Ryzhov, Ziru Li","doi":"10.1152/ajpendo.00521.2024","DOIUrl":"10.1152/ajpendo.00521.2024","url":null,"abstract":"<p><p>Obesity is a global health challenge associated with significant metabolic and cardiovascular risks. Bariatric surgery and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective interventions for weight loss and metabolic improvement, yet their comparative effects on systemic metabolism-particularly energy metabolism, bone health, and heart function-remain unclear. In this study, obese male mice underwent vertical sleeve gastrectomy (VSG), 6 wk of GLP-1RA (semaglutide) treatment, or sham procedure with saline injection as controls. Dynamic changes in body weight, food intake, fat mass, lean mass, and bone mineral density were monitored. Energy metabolism was assessed using indirect calorimetry. Bone parameters and heart function were evaluated by microcomputed tomography or echocardiography, respectively. Compared with obese controls, VSG and semaglutide treatment comparably reduced body weight and improved glucose metabolism. However, VSG decreased energy expenditure, whereas both treatments similarly promoted lipid utilization. Semaglutide treatment increased ambulatory activity during nighttime. VSG led to significant bone loss, although 6 wk of semaglutide treatment had no significant effects on the skeleton. Cardiovascular outcomes also differed: VSG increased stroke volume without altering heart mass, whereas semaglutide reduced heart mass and transiently elevated heart rate. These findings underscore the importance of carefully weighing the benefits and potential risks of different weight loss treatments when addressing obesity and its systemic complications.<b>NEW & NOTEWORTHY</b> Comparative studies of surgical and pharmaceutical approaches to weight loss offer critical insights that can guide clinical decision-making for managing obesity. VSG and semaglutide exhibit comparable efficacy in promoting weight reduction and improving glucose metabolism. VSG reduces energy expenditure, whereas semaglutide increases animal activity during nighttime. VSG leads to significant bone loss, whereas semaglutide preserves bone mass independent of weight loss. VSG improves cardiac outcomes, whereas semaglutide transiently affects heart function.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E555-E566"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613027","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":"Corrigendum for Galsgaard et al., volume 328, 2025, p. E435-E446.","authors":"","doi":"10.1152/ajendo.00437.2024_COR","DOIUrl":"10.1152/ajendo.00437.2024_COR","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"328 4","pages":"E652"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802248","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":"Dehydration-induced AVP stimulates glucagon release and ketogenesis.","authors":"Thomas G Hill, Linford J B Briant, Angela Kim, Yanling Wu, Patrik Rorsman, Ingrid Wernstedt Asterholm, Anna Benrick","doi":"10.1152/ajpendo.00505.2024","DOIUrl":"10.1152/ajpendo.00505.2024","url":null,"abstract":"<p><p>Gliflozins, such as dapagliflozin, belong to a class of drugs that inhibit the sodium-glucose cotransporter 2. Gliflozins have been found to raise glucagon levels, a hormone secreted from pancreatic islet α-cells, which can trigger ketosis. However, the precise mechanisms through which gliflozins increase glucagon secretion remain poorly understood. In addition, gliflozins induce osmotic diuresis, resulting in increased urine volume and plasma osmolality. In this study, we investigated the hypothesis that a compensatory increase in arginine-vasopressin (AVP) mediates dapagliflozin-induced increases in glucagon in vivo. We show that dapagliflozin does not increase glucagon secretion in the perfused mouse pancreas, neither at clinical nor at supra-clinical doses. In contrast, AVP potently increases glucagon secretion. In vivo, dapagliflozin increased plasma glucagon, osmolality, and AVP. An oral load with hypertonic saline amplified dapagliflozin-induced glucagon secretion. Notably, a similar increase in glucagon could also be elicited by dehydration, evoked by 24-h water restriction. Conversely, blockade of vasopressin 1b receptor signaling, with either pharmacological antagonism or knockout of the receptor, resulted in reduced dapagliflozin-induced glucagon secretion in response to both dapagliflozin and dehydration. Finally, blocking vasopressin 1b receptor signaling in a mouse model of type 1 diabetes diminished the glucagon-promoting and ketogenic effects of dapagliflozin. Collectively, our data suggest that AVP is an important regulator of glucagon release during both drug-induced and physiological dehydration.<b>NEW & NOTEWORTHY</b> Gliflozin-induced ketogenic effects partly result from increased glucagon levels. This study shows that dapagliflozin-triggered glucagon secretion is not directly mediated by the pancreas but rather linked to arginine-vasopressin (AVP). Dehydration, common in diabetic ketoacidosis, elevates AVP, potentially explaining the increased ketoacidosis risk in gliflozin-treated patients. Thus, our results highlight AVP as a potential therapeutic target to mitigate the risk of ketoacidosis associated with gliflozin treatments in patients with diabetes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E633-E644"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of steatosis and fibrosis in mice on a MASH-inducing diet and the effects of housing temperature.","authors":"Neil B Blok, Andriy Myronovych, Garrett McMahon, Nadejda Bozadjieva-Kramer, Randy J Seeley","doi":"10.1152/ajpendo.00401.2024","DOIUrl":"10.1152/ajpendo.00401.2024","url":null,"abstract":"<p><p>Obesity induction in mice requires high-fat diet exposure. Although hepatic steatosis develops, progression to inflammation and fibrosis, as in humans, requires prolonged exposure and additional dietary factors. Immunosuppression at room temperature may slow this progression. We evaluated thermoneutrality's effect on metabolic dysfunction-associated steatohepatitis (MASH) development using a fibrosis-inducing MASH [Gubra-Amylin NASH (GAN)] diet. Mice were fed either a MASH or chow diet and housed at room temperature or thermoneutrality. MASH diet groups were euthanized monthly from 4 to 7 mo. Serum markers of hepatic function were analyzed, and liver histology assessed steatosis, inflammation, ballooning [nonalcoholic fatty liver disease activity score (NAS) score], and fibrosis via Picrosirius Red staining. MASH diet increased body weight, liver-to-body mass ratio, and hepatic fat, with no difference between housing conditions. Housing temperature had minimal effects on MASH. Serum markers and hepatic fibrosis were similar across groups. NAS score was lower at 4 mo in thermoneutral MASH mice but not by 7 mo. Thermoneutrality did not significantly impact MASH development. These findings, alongside existing literature, suggest thermoneutral housing does not consistently enhance MASH progression in GAN MASH-fed mice.<b>NEW & NOTEWORTHY</b> The development of MASH in mice-does housing temperature make a real difference?</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E513-E523"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490535","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":"Mammary tumor development induces perturbation of liver glucose metabolism with inflammation and fibrosis.","authors":"Anouk Charlot, Anthony Bringolf, Joris Mallard, Amélie Jaulin, Emilie Crouchet, Anne-Laure Charles, Delphine Duteil, Fabien Alpy, Catherine-Laure Tomasetto, Thomas F Baumert, Joffrey Zoll","doi":"10.1152/ajpendo.00498.2024","DOIUrl":"10.1152/ajpendo.00498.2024","url":null,"abstract":"<p><p>Cancer cells rely on glycolysis and lactic fermentation for ATP production, inducing an abnormal glucose uptake in tumors. However, it is largely unknown whether the increased tumor glucose consumption affects overall body glucose homeostasis including perturbation of the liver glucose production pathways. The effect of mammary tumor development on the liver metabolism pathway was examined by using a mouse model based on FVB/N wild-type (WT-SD) and FVB/N-Tg(MMTV-PyVT)634Mul/J mice (Tg-SD), who develop spontaneous mammary tumors. Blood and livers were analyzed for metabolic changes, by measuring histological staining, signaling, and insulin sensitivity. Tg-SD mice developed mammary tumors with an average weight of 6 g, and cancer development increased total food intake without impacting body weight gain. Tumor development did not affect blood glycemia and lactate levels but increased insulin and homeostasis model assessment of insulin resistance (HOMA-IR) index (<i>P</i> = 0.06). In the liver, Tg-SD mice with tumors exhibited a decrease in glycogen content and an increase in gluconeogenesis gene expression, as G6pc, Pgc1α, and Foxo1 (<i>P</i> < 0.05), as well as Pepck and Ldha (<i>P</i> < 0.01). Moreover, the phosphorylation of AMPK and AKT was significantly decreased (<i>P</i> < 0.01 and <i>P</i> < 0.05, respectively). Surprisingly, liver fibrosis was markedly increased in Tg mice (<i>P</i> < 0.05) alongside elevated inflammatory gene expression, such as IL1β (<i>P</i> < 0.01) or IL6 (<i>P</i> < 0.05). Here, we found that the development of non-metastatic mammary tumors using the MMTV-PyMT mouse model disrupts liver function through the development of inflammation, fibrosis, and metabolic perturbation, including an increase in glucose production and insulin resistance. Finally, these observations unravel a previously unknown metabolic cross talk between the tumors and the liver.<b>NEW & NOTEWORTHY</b> This work demonstrates that the spontaneous development of non-metastatic mammary tumors triggers hepatic activation of endogenous glucose production pathways, coinciding with the onset of insulin resistance. This finding suggests a significant cross talk between tumors and the liver during tumorigenesis, aiming at enhancing glucose production to meet the elevated energy demands of the tumor. Understanding this interaction could provide insights into metabolic alterations associated with cancer and lead to potential therapeutic targets to inhibit tumor metabolism.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E645-E651"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662039","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":"A specific metabolomic and lipidomic signature reveals the postpartum resolution of gestational diabetes mellitus or its evolution to type 2 diabetes in rat.","authors":"Paul Bobin, Delphine Mitanchez, Blandine Castellano, Isabelle Grit, Thomas Moyon, Axel Raux, Anne Vambergue, Norbert Winer, Dominique Darmaun, Catherine Michel, Gwenola Le Drean, Marie-Cécile Alexandre-Gouabau","doi":"10.1152/ajpendo.00396.2024","DOIUrl":"10.1152/ajpendo.00396.2024","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) represents a major public health concern due to adverse maternal postpartum and long-term outcomes. Current strategies to manage GDM fail to reduce the maternal risk to develop later impaired glucose tolerance (IGT) and type 2 diabetes (T2D). In a rodent model of diet-induced GDM without obesity, we explored the perinatal metabolic adaptations in dams with gestational IGT followed by either persistent or resolved postpartum IGT. Female Sprague-Dawley rats were fed a high-fat high-sucrose (HFHS) or a chow [control group (CTL)] diet, 1 wk before mating and throughout gestation (G). Following parturition, HFHS dams were randomized to two subgroups: one switched to a chow diet and the other one maintained on an HFHS diet throughout lactation (L). Oral glucose tolerance tests (OGTTs) were performed, and plasma metabolome-lipidome were characterized at G12 and L12. We found that <i>1</i>) in GDM-pregnant dams, IGT was associated with incomplete fatty acid oxidation (FAO), enhanced gluconeogenesis, altered insulin signaling, and oxidative stress; <i>2</i>) improved glucose tolerance postpartum seemed to restore complete FAO along with elevation of nervonic acid-containing sphingomyelins, assumed to impart β-cell protection; and <i>3</i>) persistence of IGT after delivery was associated with metabolites known to predict the early onset of insulin and leptin resistance, with maintained liver dysfunction. Our findings shed light on the impact of postpartum IGT evolution on maternal metabolic outcome after an episode of GDM. They suggest innovative strategies, implemented shortly after delivery and targeted on these biomarkers, should be explored to curb or delay the transition from GDM to T2D in these mothers.<b>NEW & NOTEWORTHY</b> Specific metabolomic/lipidomic features are associated with GDM postpartum outcomes. GDM-pregnant dams exhibit partial fatty acid oxidation and boosted gluconeogenesis. Resolution of postpartum IGT relies on nervonic acid-sphingomyelin, a β-cell protector. Postpartum IGT persistence suggests muscle insulin resistance and liver dysfunction.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E493-E512"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412968","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":"Plasma complement system markers and their association with cardiometabolic risk factors: an ethnic comparison of White European and Black African men.","authors":"Reuben M Reed, Wioleta M Zelek, B Paul Morgan, Gráinne Whelehan, Sam Lockhart, Stephen O'Rahilly, Oliver C Witard, Martin B Whyte, Louise M Goff","doi":"10.1152/ajpendo.00419.2024","DOIUrl":"10.1152/ajpendo.00419.2024","url":null,"abstract":"<p><p>Populations of Black African (BA) ancestry are disproportionately affected by cardiometabolic diseases, possibly due to dysregulation of the complement system. This study aimed to determine relationships between fasting complement markers and cardiometabolic risk in BA and White European (WE) men, and whether postprandial complement response differs by ethnicity. Eighty-eight BA and 97 WE men [age = 44.4 (42.0-47.6) yr, body mass index (BMI) = 29.2 ± 4.5 kg·m^-2] were assessed for fasting plasma complement markers and cardiometabolic risk factors. A second cohort (<i>n</i> = 20 men, 10 BA) [age = 31.0 ± 1.1 yr, BMI = 27.1 (26.0-28.6) kg·m^-2] men underwent a moderate-to-high-fat feeding protocol to measure postprandial plasma complement, serum insulin, plasma glucose, triacylglycerol (TAG), and nonesterified fatty acids. C4 and Factor D were lower, and iC3b was higher in BA compared with WE men. C3 and C4 were strongly associated with all adiposity markers in both ethnicities, but the WE cohort showed stronger associations between C3 and subcutaneous adipose tissue, C5 and WC, and iC3b and visceral adipose tissue compared with BA. C3 was associated with all cardiometabolic risk factors in both ethnicities. Associations between C5 and cholesterol, C4 and TAG, and terminal complement complex and (both total and LDL)-cholesterol were only observed in the WE cohort. There was a trend toward ethnic differences in postprandial Factor D (<i>P</i> = 0.097) and iC3b (<i>P</i> = 0.085). The weaker associations between the complement system markers with adiposity and lipid profiles in BA compared with WE men suggest ethnic differences in the determinants of complement production and activation, whereby adipose tissue may play a less important role in BA men.<b>NEW & NOTEWORTHY</b> The present study found that markers of the complement system were less strongly associated with adiposity and lipid profiles in Black African men compared with White European men, suggesting ethnic differences in the determinants of complement production and activation. In Black African men, adipose tissue may play a less important role in complement production and activation and also in the link with traditional cardiometabolic risk factors.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E611-E619"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565782","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}