scholarly journals TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandre Moura-Assis ◽  
Pedro A. S. Nogueira ◽  
Jose C. de-Lima-Junior ◽  
Fernando M. Simabuco ◽  
Joana M. Gaspar ◽  
...  
Keyword(s):  
Dietary Fats ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Hypothalamic Inflammation ◽  
Novel Target ◽  
Tlr4 Activation ◽  
Leucine Rich Repeats ◽  
Body Energy

AbstractObesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalamic inflammation remains unknown. Here, we demonstrate that the knockdown of TLR4-interactor with leucine-rich repeats (Tril), a functional component of TLR4, resulted in reduced hypothalamic inflammation, increased whole-body energy expenditure, improved the systemic glucose tolerance and protection from diet-induced obesity. The POMC-specific knockdown of Tril resulted in decreased body fat, decreased white adipose tissue inflammation and a trend toward increased leptin signaling in POMC neurons. Thus, Tril was identified as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental obesity and its inhibition in the hypothalamus may represent a novel target for obesity treatment.

scholarly journals POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness

2020 ◽  
Author(s):  
Alexandre Moura-Assis ◽  
Pedro A. Nogueira ◽  
Jose C. de-Lima-Junior ◽  
Fernando M. Simabuco ◽  
Joana M. Gaspar ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Arcuate Nucleus ◽  
Whole Body ◽  
Potential Candidate ◽  
Diet Induced Obesity ◽  
Body Adiposity ◽  
Hypothalamic Inflammation ◽  
Leucine Rich Repeats ◽  
Body Energy ◽  
Harmful Effects

AbstractIn a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.

scholarly journals The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Jamie I. van der van der Vaart ◽  
Mariëtte R. Boon ◽  
Riekelt H. Houtkooper
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Ampk Signaling ◽  
Mitochondrial Homeostasis ◽  
Brown Adipose ◽  
Metabolic Stresses ◽  
Amp Activated Protein Kinase ◽  
Body Energy

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

Abstract 1766: Diet-Induced Obesity Causes Inflammation by Activating Toll-Like Receptor 4 Signaling and Downregulates AMPK in Heart

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hwi Jin Ko ◽  
Dae Young Jung ◽  
Zhexi Ma ◽  
Jason K Kim
Keyword(s):  
Glucose Metabolism ◽  
Whole Body ◽  
Chow Diet ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Myocardial Glucose Metabolism ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Diet Induced Obesity

Increasing evidence implicates the role of inflammation in diabetes and complications. Macrophages are shown to infiltrate adipose tissue in obesity, and inflammatory cytokines alter glucose metabolism in peripheral organs. Male C57BL/6 mice were fed high-fat diet (HFD; 55% fat by calories) or chow diet for 6 weeks, and heart samples were taken for analysis (n = 5~7). Chronic HFD increased whole body fat mass, measured by 1 H-MRS, by 3-fold, and elevated plasma IL-6 and TNF-α levels by 40%. Diet-induced obesity caused inflammation in heart and increased macrophage-specific CD68 levels by 5-fold (Fig. 1) (* P < 0.05 vs Chow). Diet-induced cardiac inflammation was associated with significant increases in toll-like receptor 4 (TLR4) and MyD88 levels in heart (Fig. 2). HFD also increased cardiomyocyte SOCS3 levels by more than 3-fold (Fig. 3). Myocardial glucose metabolism was measured using intravenous injection of 2-[ 14 C]deoxyglucose in awake mice (n = 6). Chronic HFD reduced myocardial glucose uptake by 50%, and this was associated with significant reductions in total GLUT4 and GLUT1 protein levels. Further, Thr 172 phosphorylation of AMPK, a critical regulator of energy balance, was markedly reduced in heart following HFD (Fig. 4). These results demonstrate that diet-induced obesity causes macrophage infiltration and inflammation in heart by increasing TLR4 signaling in cardiomyocytes. Similar to the effects of inflammation on peripheral glucose metabolism, diet-induced cardiac inflammation reduced myocardial glucose metabolism by downregulating AMPK and GLUT protein levels. Thus, our findings underscore an important role of inflammation in diabetic heart.

scholarly journals Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

2020 ◽  
Vol 375 (1793) ◽  
pp. 20190135 ◽  
Author(s):  
Naresh C. Bal ◽  
Muthu Periasamy
Keyword(s):  
Energy Homeostasis ◽  
Atp Hydrolysis ◽  
Calcium Atpase ◽  
Whole Body ◽  
Signalling Molecule ◽  
Brown Adipose ◽  
Pump Activity ◽  
Body Energy ◽  
Shivering Thermogenesis

Thermogenesis in endotherms relies on both shivering and non-shivering thermogenesis (NST). The role of brown adipose tissue (BAT) in NST is well recognized, but the role of muscle-based NST has been contested. However, recent studies have provided substantial evidence for the importance of muscle-based NST in mammals. This review focuses primarily on the role of sarcoplasmic reticulum (SR) Ca 2+ -cycling in muscle NST; specifically, it will discuss recent data showing how uncoupling of sarcoendoplasmic reticulum calcium ATPase (SERCA) (inhibition of Ca 2+ transport but not ATP hydrolysis) by sarcolipin (SLN) results in futile SERCA pump activity, increased ATP hydrolysis and heat production contributing to muscle NST. It will also critically examine how activation of muscle NST can be an important factor in regulating metabolic rate and whole-body energy homeostasis. In this regard, SLN has emerged as a powerful signalling molecule to promote mitochondrial biogenesis and oxidative metabolism in muscle. Furthermore, we will discuss the functional interplay between BAT and muscle, especially with respect to how reduced BAT function in mammals could be compensated by muscle-based NST. Based on the existing data, we argue that SLN-mediated thermogenesis is an integral part of muscle NST and that muscle NST potentially contributed to the evolution of endothermy within the vertebrate clade. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

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

Role of alpha- and beta-adrenoceptors in sympathetically mediated thermogenesis

1993 ◽  
Vol 264 (1) ◽  
pp. E11-E17 ◽  
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
K. P. Kempen ◽  
W. H. Saris
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Energy Expenditure ◽  
Whole Body ◽  
Healthy Male ◽  
Beta Adrenoceptor ◽  
Beta 2 ◽  
Body Energy ◽  
Stimulation Of

This study was intended to investigate the role of alpha- and beta-adrenoceptor populations in the sympathetically mediated thermogenesis in healthy lean males. In the first study, the beta 1-, beta 2-, and beta 3-agonist isoprenaline was infused in increasing doses with and without simultaneous infusion of the beta 1-blocker atenolol (Iso and Iso+AT, respectively). There was an increase in whole body energy expenditure (EE) after infusing Iso+AT (P < 0.001) and an almost twofold higher increase after infusion of Iso only (P < 0.001). Stimulation of the beta 2-adrenoceptors by a specific agonist (salbutamol) resulted in a significant increase in EE (P < 0.001). The effect of stimulation of alpha 1-adrenoceptors on EE was measured by infusing increasing doses of the alpha 1-agonist phenylephrine. EE did not change, whereas blood pressure (BP) increased (P < 0.001) and heart rate decreased (P < 0.01). In addition to this study, the alpha 1-, alpha 2-, beta 1-, beta 2-, and beta 3-agonists norepinephrine and epinephrine were infused with simultaneous infusion of the beta 1- and beta 2-blocker propranolol. In both studies, there was no effect on EE, whereas BP increased (P < 0.01). In conclusion, in healthy male lean volunteers both beta 1- and beta 2-adrenoceptors are involved in the sympathetically mediated thermogenesis, whereas the alpha 1-, alpha 2-, and beta 3-adrenoceptors do not play a role.

scholarly journals The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Romain Girard ◽  
Sarah Tremblay ◽  
Christophe Noll ◽  
Stéphanie St-Jean ◽  
Christine Jones ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Diet Induced Obesity ◽  
Regulatory Circuit ◽  
Body Energy

AbstractThe transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

Sign in / Sign up

Export Citation Format

Share Document