Quantification of the Immunometabolite Protein Modifications S-2-Succinocysteine and 2,3- Dicarboxypropylcysteine
Am J Physiol Endocrinol Metab. 2024 Feb 7. doi: 10.1152/ajpendo.00354.2023. Online ahead of print.ABSTRACTThe tricarboxylic acid (TCA) cycle metabolite fumarate non-enzymatically reacts with the amino acid cysteine to form S-(2-succino)cysteine (2SC), referred to as protein succination. The immunometabolite itaconate accumulates during lipopolysaccharide (LPS) stimulation of macrophages and microglia. Itaconate non-enzymatically reacts with cysteine residues to generate 2,3-dicarboxypropylcysteine (2,3-DCP), referred to as protein dicarboxypropylation. Since fumarate and itaconate levels dynamically change in activated imm...
Source: Am J Physiol Endocri... - February 7, 2024 Category: Endocrinology Authors: J Hunter Cox Richard S McCain Emery Tran Shoba Swaminathan Holland H Smith Gerardo G Piroli Michael Shtutman Michael D Walla William E Cotham Norma Frizzell Source Type: research
Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice
This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to th...
Source: Am J Physiol Endocri... - January 31, 2024 Category: Endocrinology Authors: Minoru Tanaka Ken Sugimoto Hiroshi Akasaka Shino Yoshida Toshimasa Takahashi Taku Fujimoto Keyu Xie Yukiko Yasunobe Koichi Yamamoto Takumi Hirabayashi Ryosuke Nakanishi Hidemi Fujino Hiromi Rakugi Source Type: research
Thiazolidinedione enhances the efficacy of immunotherapy in murine melanoma
Am J Physiol Endocrinol Metab. 2024 Jan 31. doi: 10.1152/ajpendo.00346.2023. Online ahead of print.ABSTRACTSeveral clinical studies observed a surprising beneficial effect of obesity to increase immunotherapy responsiveness in melanoma patients, highlighting an as-yet insufficiently understood relationship between metabolism and immunogenicity. Here we demonstrate that the thiazolidinedione (TZD) rosiglitazone, a drug used to treat diabetes by sequestering fatty acids in the metabolically inert subcutaneous adipose tissue, improved sensitivity to anti-Programmed Cell Death Protein 1 (PD-1) treatment in YUMMER1.7 tumor-bear...
Source: Am J Physiol Endocri... - January 31, 2024 Category: Endocrinology Authors: Xinyi Zhang Yuan Gao Keyun Tang Zongyu Li Alexandra A Halberstam Liqun Zhou Rachel J Perry Source Type: research
Metabolic underpinnings of cancer-related fatigue
Am J Physiol Endocrinol Metab. 2024 Jan 31. doi: 10.1152/ajpendo.00378.2023. Online ahead of print.ABSTRACTCancer-related fatigue (CRF) is one of the most prevalent and detrimental complications of cancer. Emerging evidence suggests that obesity and insulin resistance are associated with CRF occurrence and severity in cancer patients and survivors. In this narrative review, we analyzed recent studies including both preclinical and clinical research on the relationship between obesity and/or insulin resistance and CRF. We also describe potential mechanisms for these relationships, though with the caveat that because the mec...
Source: Am J Physiol Endocri... - January 31, 2024 Category: Endocrinology Authors: Xinyi Zhang Rachel J Perry Source Type: research
Chronic cortisol-stimulation enhances hypothalamus-specific enrichment of metabolites in the rainbow trout brain
Am J Physiol Endocrinol Metab. 2024 Jan 31. doi: 10.1152/ajpendo.00410.2023. Online ahead of print.ABSTRACTThe hypothalamus is a key integrating centre that is involved in the initiation of the corticosteroid stress response, and in regulating nutrient homeostasis. While cortisol, the principal glucocorticoid in humans and teleosts, plays a central role in the feeding regulation, the mechanisms are far from clear. We tested the hypothesis that the metabolic changes to cortisol exposure signal an energy excess in the hypothalamus, leading to feeding suppression during stress in fish. Rainbow trout (Oncorhynchus mykiss) were...
Source: Am J Physiol Endocri... - January 31, 2024 Category: Endocrinology Authors: Ayelen M Blanco Femilarani Antomagesh Sara Comesa ña Jose L Soengas Mathilakath M Vijayan Source Type: research
Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function
In this report, we examined pH regulation of the Golgi and identified a partial alkalinization of the Golgi lumen in a diabetes model. To further explore this, we generated a β-cell specific knockout (KO) of the v0a2 subunit of the v-ATPase pump, which anchors the v-ATPase to the Golgi membrane. Although loss of v0a2 partially neutralized Golgi pH and was accompanied by distension of the Golgi cisternae, proinsulin export from the Golgi and insulin granule formation were not affected. Furthermore, β-cell function was well preserved. β-cell v0a2 KO mice exhibited normal glucose tolerance in both sexes, no genotypic diffe...
Source: Am J Physiol Endocri... - January 24, 2024 Category: Endocrinology Authors: Cierra K Boyer Sandra E Blom Ashleigh E Machado Kristen E Rohli Michelle E Maxson Samuel B Stephens Source Type: research
The Impact of Glucagon to Support Post-Absorptive Glucose Flux and Glycemia in Healthy Rats and its Attenuation in Male Zucker Diabetic Fatty Rats
Am J Physiol Endocrinol Metab. 2024 Jan 24. doi: 10.1152/ajpendo.00192.2023. Online ahead of print.ABSTRACTHyperglucagonemia is a hallmark of type 2 diabetes (T2DM), yet the role of elevated plasma glucagon (P-GCG) to promote excessive post-absorptive glucose production and contribute to hyperglycemia in patients with this disease remains debatable. We investigated the acute action of P-GCG to safeguard/support post-absorptive endogenous glucose production (EGP) and euglycemia in healthy Zucker control lean (ZCL) rats. Using male Zucker diabetic fatty (ZDF) rats that exhibit the typical metabolic disorders of human T2DM, s...
Source: Am J Physiol Endocri... - January 24, 2024 Category: Endocrinology Authors: Shanea K Estes Chiyo Shiota Tracy P O'Brien Richard L Printz Masakazu Shiota Source Type: research
Heme-based oxygen gasoreceptors
Am J Physiol Endocrinol Metab. 2024 Feb 1;326(2):E178-E181. doi: 10.1152/ajpendo.00004.2024. Epub 2024 Jan 17.ABSTRACTTo investigate gasocrine signaling, there is a critical need to identify gasoreceptors for the essential gasotransmitters like O2. Based on existing scientific literature, I propose that heme-based O2 sensors, featuring diverse signaling domains across genera, should be explicitly designated as O2 gasoreceptors. Acknowledging that O2 gasoreceptors are likely to belong to multiple protein classes with diverse signaling domains and pathways will facilitate a comprehensive search for O2 gasoreceptors in all or...
Source: Am J Physiol Endocri... - January 17, 2024 Category: Endocrinology Authors: Savani Anbalagan Source Type: research
The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E277-E289. doi: 10.1152/ajpendo.00345.2023. Epub 2024 Jan 17.ABSTRACTAlthough the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration [i.e., pharmacologically lowering circulating nonesterified fatty acid (NEFA) availability] on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age: 22 ± 1 years; body mass index: 24.0 ± 0.6 kg·m-2) underwent 2 ...
Source: Am J Physiol Endocri... - January 17, 2024 Category: Endocrinology Authors: Marlou L Dirks Tom S O Jameson Rob C Andrews Mandy V Dunlop Doaa R Abdelrahman Andrew J Murton Benjamin T Wall Francis B Stephens Source Type: research
Maternal GLP-1 receptor activation inhibits fetal growth
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E268-E276. doi: 10.1152/ajpendo.00361.2023. Epub 2024 Jan 10.ABSTRACTGlucagon-like peptide 1 (GLP-1) regulates food intake, insulin production, and metabolism. Our recent study demonstrated that pancreatic α-cells-secreted (intraislet) GLP-1 effectively promotes maternal insulin secretion and metabolic adaptation during pregnancy. However, the role of circulating GLP-1 in maternal energy metabolism remains largely unknown. Our study aims to investigate systemic GLP-1 response to pregnancy and its regulatory effect on fetal growth. Using C57BL/6 mice, we observed a gradual d...
Source: Am J Physiol Endocri... - January 10, 2024 Category: Endocrinology Authors: Liping Qiao Cindy Lu Tianyi Zang Brianna Dzyuba Jianhua Shao Source Type: research
Oocyte and cumulus cell cooperativity and metabolic plasticity under the direction of oocyte paracrine factors
Am J Physiol Endocrinol Metab. 2024 Jan 10. doi: 10.1152/ajpendo.00148.2023. Online ahead of print.ABSTRACTMammalian oocytes develop and mature in a mutually dependent relationship with surrounding cumulus cells. The oocyte actively regulates cumulus cell differentiation and function by secreting soluble paracrine oocyte-secreted factors (OSFs). We characterized the molecular mechanisms by which two model OSFs, cumulin and BMP15, regulate oocyte maturation and cumulus-oocyte cooperativity. Exposure to these OSFs during mouse oocyte maturation in vitro altered the proteomic and multispectral autofluorescence profiles of bot...
Source: Am J Physiol Endocri... - January 10, 2024 Category: Endocrinology Authors: Dulama Richani Anne Poljak Baily Wang Saabah B Mahbub Joanna Biazik Jared M Campbell Abbas Habibalahi William A Stocker Maria B Marinova Brett Nixon Sonia Bustamante David Skerrett-Byrne Craig A Harrison Ewa Goldys Robert B Gilchrist Source Type: research
17 α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E226-E244. doi: 10.1152/ajpendo.00215.2023. Epub 2024 Jan 10.ABSTRACT17α-estradiol (17α-E2) is a naturally occurring nonfeminizing diastereomer of 17β-estradiol that has life span-extending effects in rodent models. To date, studies of the systemic and tissue-specific benefits of 17α-E2 have largely focused on the liver, brain, and white adipose tissue with far less focus on skeletal muscle. Skeletal muscle has an important role in metabolic and age-related disease. Therefore, this study aimed to determine whether 17α-E2 treatment has positive, tissue-specific effects o...
Source: Am J Physiol Endocri... - January 10, 2024 Category: Endocrinology Authors: Matthew P Bubak Shivani N Mann Agnieszka K Borowik Atul Pranay Albert Batushansky Ivo Vieira de Sousa Neto Samim A Mondal Stephen M Doidge Arik Davidyan Marcelina M Szczygiel Frederick F Peelor Sandra Rigsby Matle E Broomfield Charles I Lacy Heather C Ric Source Type: research
Human liver afferent and efferent nerves revealed by 3-D/Airyscan super-resolution imaging
Am J Physiol Endocrinol Metab. 2024 Feb 1;326(2):E107-E123. doi: 10.1152/ajpendo.00205.2023. Epub 2024 Jan 3.ABSTRACTNeural regulation of hepatic metabolism has long been recognized. However, the detailed afferent and efferent innervation of the human liver has not been systematically characterized. This is largely due to the liver's high lipid and pigment contents, causing false-negative (light scattering and absorption) and false-positive (autofluorescence) results in in-depth fluorescence imaging. Here, to avoid the artifacts in three-dimensional (3-D) liver neurohistology, we embed the bleached human liver in the high-...
Source: Am J Physiol Endocri... - January 3, 2024 Category: Endocrinology Authors: Chien-Chia Chen Shih-Jung Peng Ya-Hsien Chou Chih-Yuan Lee Po-Huang Lee Rey-Heng Hu Ming-Chih Ho Mei-Hsin Chung Fu-Ting Hsiao Yu-Wen Tien Shiue-Cheng Tang Source Type: research
Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E207-E214. doi: 10.1152/ajpendo.00285.2023. Epub 2024 Jan 3.ABSTRACTMitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned ...
Source: Am J Physiol Endocri... - January 3, 2024 Category: Endocrinology Authors: Hiroshi Kumagai Su-Jeong Kim Brendan Miller Toshiharu Natsume Junxiang Wan Michi Emma Kumagai Ricardo Ramirez Shin Hyung Lee Ayaka Sato Hemal H Mehta Kelvin Yen Pinchas Cohen Source Type: research
Empagliflozin improves vascular insulin sensitivity and muscle perfusion in persons with type 2 diabetes
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E258-E267. doi: 10.1152/ajpendo.00267.2023. Epub 2024 Jan 3.ABSTRACTSodium glucose cotransporter 2 inhibitors (SGLT2is) improved major adverse cardiovascular events (MACE), heart failure, and renal outcomes in large trials; however, a thorough understanding of the vascular physiological changes contributing to these responses is lacking. We hypothesized that SGLT2i therapy would diminish vascular insulin resistance and improve hemodynamic function, which could improve clinical outcomes. To test this, we treated 11 persons with type 2 diabetes for 12 wk with 10 mg/day empagli...
Source: Am J Physiol Endocri... - January 3, 2024 Category: Endocrinology Authors: Linda A Jahn Lee M Hartline Thi Nguyen Kevin Aylor William B Horton Zhenqi Liu Eugene J Barrett Source Type: research
