Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration

Bae, Ji‐Young; Ricciardi, Carolyn J.; Esposito, Débora; Komarnytsky, Slavko; Hu, Pan; Curry, Benjamin J.; Brown, P. S.; Gao, Zhan‐Guo; Biggerstaff, John; Chen, Jiangang; Zhao, Ling

doi:10.1152/ajpcell.00249.2013

Cited by 71 publications

(73 citation statements)

References 55 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found a reduced expression of brown genes in mice chronically infused with low-dose LPS (Figure 3) and, in agreement with a recent publication [10], we report the gene expression of the LPS sensing receptor TLR4 by brown adipocytes (Figure 5). Thus, brown adipocytes are probably capable of sensing LPS, but we did not find a direct effect of LPS in mature BAT cells in vitro.…”

Section: Discussionsupporting

confidence: 92%

“…White adipocytes express TLR4 [6] and are, as such, important immunomodulators. In recent reports, immortalized murine brown adipocytes were reported to express TLR4 and cytokine production when stimulated with LPS [10,11]. …”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it was recently shown that reduced browning of white adipose tissue is directly regulated by macrophages docking on adipocytes via integrin α 4 and its receptor vascular cell adhesion protein 1 [16]. Additionally, UCP1 was recently shown to be downregulated in brown adipocytes treated with LPS [10]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inflammation Downregulates UCP1 Expression in Brown Adipocytes Potentially via SIRT1 and DBC1 Interaction

Nøhr

Bobba

Richelsen

et al. 2017

IJMS

View full text Add to dashboard Cite

Brown adipose tissue thermogenesis at the cost of energy is not only important for the development of obesity, but also possesses great promise in anti-obesity treatment. Uncoupling protein 1 (UCP1) expression has been reported to be under control of the intracellular deacetylase SIRT1. Here, we investigated the effect and mechanism of inflammation and sirtuin-1 (SIRT1) activation on the induction of thermogenic genes in immortalized brown adipocytes incubated with LPS or IL1β and mice with elevated inflammatory tone. In vitro stimulation of brown adipocytes with dibutyryl cyclic adenosine monophosthate (dbcAMP) reduced the expression of deleted in breast cancer-1 (Dbc1) (SIRT1 inhibitor) and increased the Ucp1 expression. Silencing of SIRT1 attenuated dbcAMP induction of Ucp1. In contrast, IL1β increased the expression of Dbc1 and greatly reduced the induction of Ucp1. Similarly, in vivo studies revealed decreased expression of Ucp1 in brown adipose tissue (BAT) in mice chronically infused with LPS. Resveratrol, a known SIRT1 activator, partly rescued the Ucp1 downregulation by inflammation in both the cell cultures and mice. Here, we describe how the expression of Ucp1 in BAT is controlled via SIRT1 and is reduced under inflammation and can be rescued by SIRT1 activation by resveratrol. We suggest the reduced UCP1 expression under inflammation is mediated by the increased expression of DBC1, which inhibits SIRT1 activity.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation Downregulates UCP1 Expression in Brown Adipocytes Potentially via SIRT1 and DBC1 Interaction

Nøhr

Bobba

Richelsen

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…Mitochondria are the power “engine” of the cell involved in numerous cellular processes including redox homeostasis, cellular signaling, development, growth, differentiation and even cell death (4–6). Leakage of protons and/or electrons from the mitochondrial electron transport chain (ETC) results in enhanced generation of ROS and subsequent mitochondrial oxidative stress and decreased efficiency of ATP production, cellular oxidative stress (7) and subsequent inflammation (8). Mitochondrial oxidative stress has been well established as a causal factor in the development of chronic diseases, such as diabetes (9–11) and obesity (12).…”

Section: Introductionmentioning

confidence: 99%

Lack of β, β‐carotene‐9′, 10′‐oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice

Guo

Hartson

et al. 2017

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope β,β-carotene-9’,10’-dioxygenase 2 (BCO2) is a carotenoid cleavage enzyme localized to the inner mitochondrial membrane in mammals. This study was aimed to assess the impact of genetic ablation of BCO2 on hepatic oxidative stress through mitochondrial function in mice. Methods and Results Liver samples from 6 week old male BCO2−/− knockout (KO) and isogenic wild-type (WT) mice were subjected to proteomics and functional activity assays. Compared to the WT, KO mice consumed more food (by 18 %) yet displayed significantly lower body weight (by 12 %). Mitochondrial proteomic results demonstrated that loss of BCO2 was associated with quantitative changes of the mitochondrial proteome mainly shown by suppressed expression of enzymes and/or proteins involved in fatty acid β–oxidation, the tricarboxylic acid cycle, and the electron transport chain (ETC). The mitochondrial basal respiratory rate, proton leak, and ETC complex II capacity were significantly elevated in the livers of KO compared to WT mice. Moreover, elevated reactive oxygen species and increased mitochondrial protein carbonylation were also demonstrated in liver of KO mice. Conclusions Loss of BCO2 induces mitochondrial hyperactivation, mitochondrial stress and changes of the mitochondrial proteome, leading to mitochondrial energy insufficiency. BCO2 appears to be critical for proper hepatic mitochondrial function.

show abstract

“…Critically, in the brain, UCPs appear to play a key role in preventing inflammation-induced depression [127] suggesting a direct link between cognition and mitochondrial function. In fact, it seems that uncoupling is tightly controlled by the immune system and inflammation generally suppressing it [128,129]. One of the ways this seems to happen is that it repurposes succinate dehydrogenase, at least in macrophage mitochondria, from generating energy to producing ROS, a process associated with an increased membrane potential and decreased uncoupling and enhanced glycolysis to provide the energy [130].…”

Section: The Importance Of Uncouplingmentioning

confidence: 99%

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

Nunn¹,

Guy²,

Bell³

2017

Int J Neurorehabilitation Eng

View full text Add to dashboard Cite

We are able to read this because of quantum and thermodynamic principles that via an inorganic proton gradient, possibly generated 4.2 billion years ago, gave rise to a system that has an awareness of time and space by using energy to integrate information. Life can be described as a dissipative system driven by an energy gradient that uses information to positively reinforce its self-sustaining structure, which in turn increases its non-linear decisional capacity. Key in the evolution of life has been stress coupled to natural selection, which usually meant an increased demand for energy. As hormesis describes the adaptive response to stress, we propose that hormesis embraces not only the evolution of life, but that of intelligence itself, as natural selection would favour systems that enhances its efficiency. A component of the hormetic response in eukaryotes is the mitochondrion, which itself relies on quantum effects such as tunnelling. This suggests that quantum effects control the stability of individual cells as well as long-lived cellular networks. Hormesis, which can be anti-inflammatory, is therefore key in maintaining the functional stability of complex systems, including the brain. In contrast, a lack of classical hormetic factors, such as physical activity, plant polyphenols, or calorie restriction, will lead to accelerated cognitive decline, which is associated with increased inflammation. However, there may be another previously unidentified factor that could also be considered hormetic, and that is thinking itself. Here we propose that the process of "thinking", and managing complex movement, induces "stress" in the neuronal system and is therefore in itself part of maintaining cognitive health and reserve throughout life. In effect, the right amount of thinking and information processing can beneficially induce adaptation, and this itself could be explainable by quantum thermodynamics.

show abstract

Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration

Cited by 71 publications

References 55 publications

Inflammation Downregulates UCP1 Expression in Brown Adipocytes Potentially via SIRT1 and DBC1 Interaction

Inflammation Downregulates UCP1 Expression in Brown Adipocytes Potentially via SIRT1 and DBC1 Interaction

Lack of β, β‐carotene‐9′, 10′‐oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

Contact Info

Product

Resources

About