scholarly journals Transcriptomes and metabolism define mouse and human MAIT cell heterogeneity

2021 ◽  
Author(s):  
Shilpi Chandra ◽  
Gabriel Ascui ◽  
Thomas Riffelmacher ◽  
Ashu Chawla ◽  
Ciro Ramirez-Suastegui ◽  
...  
Keyword(s):  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Developmental Pathway ◽  
Peripheral Tissues ◽  
Mait Cells ◽  
Metabolic States ◽  
Single Cell Rna Sequencing ◽  
Circulating Lymphocytes ◽  
And Storage ◽  
Mait Cell

Mucosal-associated invariant T (MAIT) cells are a subpopulation of T lymphocytes that respond to microbial metabolites. We performed single-cell RNA sequencing and metabolic analyses of MAIT cell subsets in thymus and peripheral tissues from mice and humans to define the heterogeneity and developmental pathway of these innate-like lymphocytes. We show that the predominant mouse subset, which produces IL-17 (MAIT17), and the subset that produces IFNγ (MAIT1), have greatly different transcriptomes and metabolic states in the thymus and periphery. A splenic MAIT subset has a transcriptome similar to circulating lymphocytes, and in mice these also are found in recent thymic emigrants, suggesting partially mature cells emigrate from the thymus. Human MAIT cells are predominantly MAIT1 cells, but have a different metabolism from their mouse counterparts with increased fatty acid uptake and storage. Although mouse and human subsets are similar in thymus, in the periphery they diverge, likely reflecting environmental influences.

scholarly journals The Endogenous Growth Hormone Secretagogue (Ghrelin) Is Synthesized and Secreted by Chondrocytes

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1285-1292 ◽  
Author(s):  
J. E. Caminos ◽  
O. Gualillo ◽  
F. Lago ◽  
M. Otero ◽  
M. Blanco ◽  
...  
Keyword(s):  
Cell Lines ◽  
Fatty Acid Uptake ◽  
Scatchard Analysis ◽  
Acid Uptake ◽  
Epiphyseal Growth Plate ◽  
Rt Pcr ◽  
Growth Hormone Secretagogue ◽  
Peripheral Tissues ◽  
Gh Secretion

Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), is a recently isolated hormone, prevalently expressed in stomach but also in other tissues such as hypothalamus and placenta. This novel acylated peptide acts at a central level to stimulate GH secretion and, notably, to regulate food intake. However, the existence of further, as yet unknown, effects or presence of ghrelin in peripheral tissues cannot be ruled out. In this report, we provide clear evidence for the expression of ghrelin peptide and mRNA in human, mouse, and rat chondrocytes. Immunoreactive ghrelin was identified by immunohistochemistry in rat cartilage, being localized prevalently in proliferative and maturative zone of the epiphyseal growth plate, and in mouse and human chondrocytic cell lines. Moreover, ghrelin mRNA was detected by RT-PCR and confirmed by Southern analysis in rat cartilage as well as in mouse and human chondrocytes cell lines. Ghrelin mRNA expression has been studied in rat along early life development showing a stable profile of expression throughout. Although ghrelin expression in chondrocytes suggests the presence of an unexpected autocrine/paracrine pathway, we failed to identify the functional GH secretagogue receptor type 1A by RT-PCR. On the other hand, binding analysis with 125I ghrelin suggests the presence of specific receptors different from the 1A isotype. Scatchard analysis revealed the presence of two receptors with respectively high and low affinity. Finally, ghrelin, in vitro, was able to significantly stimulate cAMP production and inhibits chondrocytes metabolic activity both in human and murine chondrocytes. In addition, ghrelin is able to actively decrease both spontaneous or insulin-induced long chain fatty acid uptake in human and mouse chondrocytes. This study is the first to provide evidence for the presence of this novel peptide in chondrocytes and suggests novel potential roles for this newly recognized component of the GH axis in cartilage metabolism.

scholarly journals Stomatin modulates adipocyte differentiation through ERK pathway and regulates lipid droplet growth and function

2020 ◽  
Author(s):  
Shao-Chin Wu ◽  
Yuan-Ming Lio ◽  
Jui-Hao Lee ◽  
Chin-Yau Chen ◽  
Tung-Wei Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Adipogenic Differentiation ◽  
Lipid Production ◽  
Fatty Acid Uptake ◽  
Major Constituent ◽  
Droplet Growth ◽  
Acid Uptake ◽  
Adipocyte Hypertrophy ◽  
And Function ◽  
And Storage

Abstract Controlling fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), are closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of the lipid raft, participate in adipogenesis and lipogenesis by preferentially recruiting effectors, such as perilipin for LD fusion or transporters for fatty acid uptake. Adipocyte-like cells having increased stomatin expressions exhibit higher levels of fatty acid uptake and LD growth or enlargements. Moreover, transgenic mice fed with a high-fat diet showed increased stomatin expression that facilitated progression of obesity and caused insulin resistance and hepatic impairments. Conversely, inhibitions of stomatin by gene knockdown or pharmacological treatments could block not only LD growth but also adipogenic differentiation through downregulation of PPARγ pathway. Effects of stomatin on PPARγ involved ERK signaling; however, an alternate pathway also exist. Amongst various anti-obesity measures, stomatin serves as another potential therapeutic target.

scholarly journals Health-Boosting Effects of Aerobic Exercise Training and Berberine on Diabetes: A Brief Overview

Thrita ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Hossein Heidari ◽  
Mohammad Ali Azarbayjani ◽  
Maghsoud Peeri ◽  
Parvin Farzanegi ◽  
Seyed Ali Hosseini
Keyword(s):  
Aerobic Exercise ◽  
Fatty Acid Uptake ◽  
Lifestyle Changes ◽  
Aerobic Exercise Training ◽  
Acid Uptake ◽  
Peripheral Tissues ◽  
Beneficial Effects ◽  
Phytochemical Compounds

: Type 2 diabetes is one of the most important metabolic disorders that affect lifestyle. Accordingly, studies have shown that lifestyle changes, especially increasing daily physical activity, can prevent diabetes and help people with the disease through various mechanisms. On the other hand, the use of medicinal plants due to having various phytochemical compounds, each of which has healing properties, can be considered a helpful method in preventing and treating diabetes complications. One of the phytochemical compounds used as an effective substance in the treatment of diabetes is an alkaloid called Berberine. Berberine has been used in traditional medicine to lower blood glucose, and new studies in both in vivo and in vitro conditions have confirmed the diabetic effect of Berberine. Receiving increased energy metabolism, increased glucose and fatty acid uptake by peripheral tissues, improving lipid profile, reducing inflammatory mediators, increasing antioxidant capacity are common mechanisms that aerobic exercise and Berberine exert their beneficial effects in diabetes. In the present study, the effect of aerobic exercise, Berberine, and its combination on diabetes markers have been investigated considering the beneficial effects of aerobic exercise and Berberine in diabetes.

Unaltered Fatty Acid Uptake, Utilization, and Mitochondrial Respiration in Right Atrial Appendage of Type 2 Diabetic Human Heart

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 335-OR
Author(s):  
NANDINI RJ ◽  
SR RAJI ◽  
VIVEK V. PILLAI ◽  
JAYAKUMAR K. ◽  
SRINIVAS GOPALA
Keyword(s):  
Fatty Acid ◽  
Mitochondrial Respiration ◽  
Human Heart ◽  
Fatty Acid Uptake ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Acid Uptake ◽  
Right Atrial Appendage ◽  
Type 2 Diabetic

scholarly journals Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

2021 ◽  
Author(s):  
Longmin Chen ◽  
Jing Zhang ◽  
Yuan Zou ◽  
Faxi Wang ◽  
Jingyi Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Macrophage Polarization ◽  
Fatty Acid Uptake ◽  
Chromatin Accessibility ◽  
Acid Uptake ◽  
High Fat ◽  
M2 Polarization ◽  
Adipose Tissue Macrophages ◽  
Cold Challenge

AbstractKdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2af/f, Kdm2a−/−) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a−/− increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a−/− mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a−/− macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a−/− mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.

scholarly journals Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
Marilyne Vandel ◽  
Bo Xiang ◽  
Vernon W. Dolinsky ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Fatty Acid Uptake ◽  
Isoquinoline Alkaloid ◽  
Acid Uptake ◽  
High Fat ◽  
Low Fat

AbstractBerberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.

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