The role of T-bet in obesity: lack of T-bet causes obesity in male mice

Kim, Kyu-Yeob; Jeong, Hyun‐Ja; Kim, Hyung-Min

doi:10.1016/j.jnutbio.2012.05.010

Cited by 8 publications

(10 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have documented that WAT resident FoxP3-expressing regulatory T cells exhibit the capacity to reverse obesity-linked insulin resistance and decrease inflammation 40,41 . Moreover mice deficient in the transcription factor responsible for the development of T helper cells, T-bet , while developing an obesogenic phenotype, exhibit hallmarks of an unhealthy metabolic profile 42 . Taken together, these studies suggest that during HFD-induced WAT expansion, MitoN-Tg sWAT harbors immune cells that promote an anti-inflammatory environment suitable for healthy WAT expansion.…”

Section: Resultsmentioning

confidence: 99%

MitoNEET-mediated effects on browning of white adipose tissue

2014

View full text Add to dashboard Cite

MitoNEET is an outer mitochondrial membrane protein that, upon overexpression in white adipose tissue (WAT), exerts a positive impact on tissue expansion and whole-body lipid and carbohydrate homeostasis by altering mitochondrial matrix iron metabolism. Here we determine the key transcriptional events in subcutaneous WAT of mice in response to mitoNEET overexpression and a high-fat diet (HFD). Microarray analyses at key points during weight gain upon body-weight divergence with wild-type mice demonstrate that mitoNEET-enriched sWAT early on upregulates a browning signature program that limits WAT expansion in transgenic mice for a period of up to 12-weeks of HFD. This compensatory browning phenotype is subsequently lost, resulting in rapid WAT expansion and body-weight gain. Exposure to thermoneutral temperatures during HFD prompts weight gain significantly earlier. Similar WAT expansion is achieved upon infection with an adeno-associated virus expressing mitoNEET. Collectively, the mitoNEET enriched fat-pads feature a more vascularized, anti-inflammatory and less fibrotic environment.

show abstract

Section: Resultsmentioning

confidence: 99%

MitoNEET-mediated effects on browning of white adipose tissue

2014

View full text Add to dashboard Cite

show abstract

“…In a high-fat-diet (HFD) model of obesity, Th1 cells are abundantly present compared to control-diet- (CD) fed mice in both subcutaneous and visceral adipose tissue (SAT, VAT) (25–28). Blocking Th1 functionality by using IFNγ and T-bet knock-out mice resulted in an attenuation of adipose tissue inflammation and better glucose tolerance (25, 45, 46) (Figure 1A). This finding was confirmed by an adoptive transfer of Th1 cells to αβ T cell-deficient HFD-fed mice (28) Interestingly, T-bet knock-out mice developed a greater total body weight and VAT mass, whereas this was not the case in IFNγ knock-out mice (25, 45, 46).…”

Section: T Helper Cellsmentioning

confidence: 99%

“…Blocking Th1 functionality by using IFNγ and T-bet knock-out mice resulted in an attenuation of adipose tissue inflammation and better glucose tolerance (25, 45, 46) (Figure 1A). This finding was confirmed by an adoptive transfer of Th1 cells to αβ T cell-deficient HFD-fed mice (28) Interestingly, T-bet knock-out mice developed a greater total body weight and VAT mass, whereas this was not the case in IFNγ knock-out mice (25, 45, 46). Notably, the metabolic alterations in T-bet-deficient mice were associated with an increased VAT expression of leptin, peroxisome proliferator receptor (PPAR) γ and CCAAT-enhancer-binding proteins (C/EBP) α (46).…”

Section: T Helper Cellsmentioning

confidence: 99%

The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity

et al. 2019

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) constitutes a spectrum of disease states characterized by hepatic steatosis and is closely associated to obesity and the metabolic syndrome. In non-alcoholic steatohepatitis (NASH), additionally, inflammatory changes and hepatocellular damage are present, representing a more severe condition, for which the treatment is an unmet medical need. Pathophysiologically, the immune system is one of the main drivers of NAFLD progression and other obesity-related comorbidities, and both the innate and adaptive immune system are involved. T cells form the cellular component of the adaptive immune system and consist of multiple differentially active subsets, i.e., T helper (Th) cells, regulatory T (Treg) cells, and cytotoxic T (Tc) cells, as well as several innate T-cell subsets. This review focuses on the role of these T-cell subsets in the pathogenesis of NAFLD, as well as the association with obesity and type 2 diabetes mellitus, reviewing the available evidence from both animal and human studies. Briefly, Th1, Th2, Th17, and Th22 cells seem to have an attenuating effect on adiposity. Th2, Th22, and Treg cells seem to decrease insulin resistance, whereas Th1, Th17, and Tc cells have an aggravating effect. Concerning NAFLD, both Th22 and Treg cells appear to have an overall tempering effect, whereas Th17 and Tc cells seem to induce more liver damage and fibrosis progression. The evidence regarding the role of the innate T-cell subsets is more controversial and warrants further exploration.

show abstract

“…While the T-bet knockout mice were expected to have increased insulin sensitivity, the finding that they were more obese, with increased visceral adiposity, was surprising, as obesity and insulin resistance are typically co-associated. Improved insulin sensitivity is perhaps due to decreased expression of Th1 cytokines and increased expression of Th2 cytokines and the Th2 transcription factor GATA binding protein 3 (GATA3) in the T-bet knockout animal (38). Moreover, adoptive transfer of T-bet-deficient CD4+ T cells, but not wildtype CD4+ T cells, into Rag2-/- mice, which lack both B and T lymphocytes, modestly improves insulin sensitivity (37).…”

Section: Obesity and Inflammationmentioning

confidence: 99%

Role of T Cells in Malnutrition and Obesity

2014

View full text Add to dashboard Cite

Nutritional status is critically important for immune cell function. While obesity is characterized by inflammation that promotes metabolic syndrome including cardiovascular disease and insulin resistance, malnutrition can result in immune cell defects and increased risk of mortality from infectious diseases. T cells play an important role in the immune adaptation to both obesity and malnutrition. T cells in obesity have been shown to have an early and critical role in inducing inflammation, accompanying the accumulation of inflammatory macrophages in obese adipose tissue, which are known to promote insulin resistance. How T cells are recruited to adipose tissue and activated in obesity is a topic of considerable interest. Conversely, T cell number is decreased in malnourished individuals, and T cells in the setting of malnutrition have decreased effector function and proliferative capacity. The adipokine leptin, which is secreted in proportion to adipocyte mass, may have a key role in mediating adipocyte-T cell interactions in both obesity and malnutrition, and has been shown to promote effector T cell function and metabolism while inhibiting regulatory T cell proliferation. Additionally, key molecular signals are involved in T cell metabolic adaptation during nutrient stress; among them, the metabolic regulator AMP kinase and the mammalian target of rapamycin have critical roles in regulating T cell number, function, and metabolism. In summary, understanding how T cell number and function are altered in obesity and malnutrition will lead to better understanding of and treatment for diseases where nutritional status determines clinical outcome.

show abstract

The role of T-bet in obesity: lack of T-bet causes obesity in male mice

Cited by 8 publications

References 27 publications

MitoNEET-mediated effects on browning of white adipose tissue

MitoNEET-mediated effects on browning of white adipose tissue

The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity

Role of T Cells in Malnutrition and Obesity

Contact Info

Product

Resources

About