scholarly journals The cell biology of fat expansion

2015 ◽  
Vol 208 (5) ◽  
pp. 501-512 ◽  
Author(s):  
Joseph M. Rutkowski ◽  
Jennifer H. Stern ◽  
Philipp E. Scherer
Keyword(s):  
Adipose Tissue ◽  
Cell Biology ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Cell Type ◽  
Metabolic Dysregulation ◽  
Organ Systems ◽  
Adipocyte Cell ◽  
Nutrient Environment ◽  
Primary Cell Type

Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

scholarly journals Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice

2019 ◽  
Vol 116 (47) ◽  
pp. 23822-23828 ◽  
Author(s):  
Shintaro Yamaguchi ◽  
Michael P. Franczyk ◽  
Maria Chondronikola ◽  
Nathan Qi ◽  
Subhadra C. Gunawardana ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Lipolytic Activity ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Adaptive Thermogenesis ◽  
Body Energy

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD+ metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD+ biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of β-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD+–SIRT1–caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD+ synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD+ biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism.

scholarly journals Regulation of Adipose Differentiation by Fructose and GluT5

2012 ◽  
Vol 26 (10) ◽  
pp. 1773-1782 ◽  
Author(s):  
Li Du ◽  
Anthony P. Heaney
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Whole Body ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Fructose Intake ◽  
Adipose Differentiation

Abstract Adipose tissue is an important metabolic organ that is crucial for whole-body insulin sensitivity and energy homeostasis. Highly refined fructose intake increases visceral adiposity although the mechanism(s) remain unclear. Differentiation of preadipocytes to mature adipocytes is a highly regulated process that is associated with characteristic sequential changes in adipocyte gene expression. We demonstrate that fructose treatment of murine 3T3-L1 cells incubated in standard differentiation medium increases adipogenesis and adipocyte-related gene expression. We further show that the key fructose transporter, GluT5, is expressed in early-stage adipocyte differentiation but is not expressed in mature adipocytes. GluT5 overexpression or knockdown increased and decreased adipocyte differentiation, respectively, and treatment of 3T3-L1 cells with a specific GluT5 inhibitor decreased adipocyte differentiation. Epidymal white adipose tissue was reduced in GluT5−/− mice compared with wild-type mice, and mouse embryonic fibroblasts derived from GluT5−/− mice exhibited impaired adipocyte differentiation. Taken together, these results demonstrate that fructose and GluT5 play an important role in regulating adipose differentiation.

scholarly journals Activated Ask1-MKK4-p38MAPK/JNK Stress Signaling Pathway in Human Omental Fat Tissue May Link Macrophage Infiltration to Whole-Body Insulin Sensitivity

2009 ◽  
Vol 94 (7) ◽  
pp. 2507-2515 ◽  
Author(s):  
Matthias Blüher ◽  
Nava Bashan ◽  
Iris Shai ◽  
Ilana Harman-Boehm ◽  
Tanya Tarnovscki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Fat Distribution ◽  
Macrophage Infiltration ◽  
Whole Body ◽  
Strongly Correlated ◽  
Jnk Pathway ◽  
Paired Samples ◽  
Adipocyte Cell ◽  
Stress Sensing

Context: Adipose tissue in obesity is thought to be exposed to various stresses, predominantly in intraabdominal depots. We recently reported that p38MAPK and Jun N-terminal kinase (JNK), but not ERK and inhibitory-κB kinase β, are more highly expressed and activated in human omental (OM) adipose tissue in obesity. Objective: The aim was to investigate upstream components of the pathways that culminate in activation of p38MAPK and JNK. Setting and Patients: Phosphorylation and expression of kinases were studied in paired samples of OM and sc adipose tissue from lean and obese subjects of two different cohorts (n = 36 and n = 196) by Western and real-time PCR analyses. The association with fat distribution, macrophage infiltration, insulin sensitivity, and glucose metabolism was assessed by correlation analyses. Results: The amount of phosphorylated forms of the kinases provided evidence for an activated stress-sensing pathway consisting of the MAP3K Ask1 (but not MLK3 or Tak1), and the MAP2Ks MKK4, 3/6, (but not MKK7), specifically in OM. OM Ask1-mRNA was more highly expressed in predominantly intraabdominally obese persons and most strongly correlated with estimated visceral fat. Diabetes was associated with higher OM Ask1-mRNA only in the lean group. In OM, macrophage infiltration strongly correlated with Ask1-mRNA, but the obesity-associated increase in Ask1-mRNA could largely be attributed to the adipocyte cell fraction. Finally, multivariate regression analyses revealed OM-Ask1 as an independent predictor of whole-body glucose uptake in euglycemic-hyperinsulinemic clamps. Conclusions: An Ask1-MKK4-p38MAPK/JNK pathway reflects adipocyte stress associated with adipose tissue inflammation, linking visceral adiposity to whole-body insulin resistance in obesity.

scholarly journals Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8308
Author(s):  
Ming-Ling Chang ◽  
Zinger Yang ◽  
Sien-Sing Yang
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Low Grade ◽  
Colon Polyps ◽  
Alcoholic Fatty Liver ◽  
Global Epidemic ◽  
Markers Of Inflammation ◽  
Digestive Diseases ◽  
Digestive Cancers

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.

scholarly journals Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Asma Ayari ◽  
Manuel Rosa-Calatrava ◽  
Steve Lancel ◽  
Johanna Barthelemy ◽  
Andrés Pizzorno ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Influenza A ◽  
Energy Homeostasis ◽  
Influenza Infection ◽  
Subcutaneous Fat ◽  
Whole Body ◽  
Glucose And Lipid Metabolism ◽  
The Impact

AbstractLike all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell’s glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infection induces alterations in whole-body glucose metabolism that persist long after the virus has been cleared. We report depot-specific changes in the WAT of IAV-infected mice, notably characterized by the appearance of thermogenic brown-like adipocytes within the subcutaneous fat depot. Importantly, viral RNA- and viral antigen-harboring cells are detected in the WAT of infected mice. Using in vitro approaches, we find that IAV infection enhances the expression of brown-adipogenesis-related genes in preadipocytes. Overall, our findings shed light on the role that the white adipose tissue, which lies at the crossroads of nutrition, metabolism and immunity, may play in influenza infection.

2006-P: The Role of Adipose Tissue-Resident Eosinophils in Adipocyte Metabolism and Whole-Body Energy Homeostasis

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2006-P ◽  
Author(s):  
TING LI ◽  
WILLIAM LESUER ◽  
ABHILASHA SINGH ◽  
JAMES D. HERNANDEZ ◽  
XIAODONG ZHANG ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Body Energy

Abstract 327: Cardiac Regulation of Metabolic Homeostasis by Med13

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Chad E Grueter ◽  
Kedryn K Baskin ◽  
Christine M Kusminski ◽  
William Holland ◽  
Philipp E Scherer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transcriptional Activation ◽  
Energy Homeostasis ◽  
The Body ◽  
Whole Body ◽  
Mediator Complex ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Metabolite Production ◽  
Body Energy

Alterations in metabolism are a major component of cardiovascular disease associated with obesity and type 2 diabetes. The complex interplay between these three diseases poses a challenge for successful treatment and warrants further studies directed at understanding the intertissue communication between major metabolic organs. We previously identified a signaling pathway within the heart that modulates systemic energy homeostasis by regulation of Med13, a component of the kinase submodule of the Mediator Complex, in the heart. The Mediator Complex is a large, multiprotein complex that functions to integrate signal specific events with transcriptional activation and elongation in a context dependent manner. Our current work further delineates a mechanism by which Med13 in the heart functions to regulate whole body energy homeostasis. The increase in energy expenditure in Med13 transgenic (TG) mice is due in part to increased triglyceride uptake and beta-oxidation in white adipose tissue and liver. Additionally, the expression of Krebs Cycle and fatty acid oxidation genes are increased in adipose tissue and liver as measured by RNA seq and in metabolite production in Med13 Tg mice. Together, these results demonstrate the Mediator Complex regulates cardiac gene expression and metabolite production which communicates with energy depots within the body to modulate whole body energy homeostasis.

scholarly journals The Impact of Single-Cell Genomics on Adipose Tissue Research

2020 ◽  
Vol 21 (13) ◽  
pp. 4773
Author(s):  
Alana Deutsch ◽  
Daorong Feng ◽  
Jeffrey E. Pessin ◽  
Kosaku Shinoda
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Diabetes Research ◽  
Obesity And Diabetes ◽  
Important Regulator ◽  
Whole Body Metabolism ◽  
Tissue Aging ◽  
The Impact

Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation.

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