KCNK3媒介のイオン流とアドレナージ信号の交響は,アディポス発熱と肥満を調節する

Yi Chen¹, Xing Zeng¹, Xuan Huang²

¹Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Cell

|October 10, 2017

まとめ

研究者らはKCNK3というカリウムチャネルを発見し茶色脂肪の適応性発熱を抑制していますこの発見によりエネルギー消費を制御し体温を維持する新しい方法が明らかになりました

科学分野:

生理学
分子生物学
メタボリズム

背景:

アドレナジック刺激はブラウンとベージュの脂肪細胞で適応的な熱生成を促します
発熱経路は知られているが,ネガティブレギュレータは十分に理解されていない.

研究の目的:

適応性発熱の新たな負の調節メカニズムを特定する.
脂肪細胞の機能とエネルギー消費の制御におけるKCNK3の役割を調査する.

主な方法:

PRDM16とKcnk3の発現を関連付けるトランスクリプション解析
ブラウンアディポサイトにおける電気生理学的研究 (カリウム流出)
アディポス特有のKcnk3ノックアウトマウスモデル.

主要な成果:

KCNK3は熱生成を否定的に調節するレオスタットとして作用する.
KCNK3はカルシウム流入を制限し,ブラウンアディポサイトにおけるアドレナージックシグナル伝達を抑制する.
Kcnk3 ノックアウトマウスはエネルギー消費が増加し肥満や低体温に抵抗します

結論:

KCNK3は,K+- Ca2+- アドレナジックシグナル伝達軸を介して,熱生成の重要な負の調節器である.
電気生理学的メカニズムは脂肪細胞の機能と組織ホメオスタシスの鍵です.
KCNK3は代謝疾患への介入の潜在的なターゲットです.

キーワード:

アドレナジック信号ブラウン脂肪カルシウムの流入 Kcnk3 について PKAシグナリング Prdm16 についてタスク"熱生成リポリス

さらに関連する動画

07:59

Measurement of Basal and Forskolin-stimulated Lipolysis in Inguinal Adipose Fat Pads

Published on: July 21, 2017

10.1K

09:20

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function

Published on: May 4, 2021

4.3K

関連する概念動画

01:25

cAMP-dependent Protein Kinase Pathways

8.6K

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

8.6K

01:26

Adrenergic Receptors: β Subtype

4.0K

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...

4.0K

01:09

GPCRs Regulate Adenylyl Cylase Activity

7.7K

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...

7.7K

01:30

Regulation of Food Intake

3.0K

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...

3.0K

01:19

Regulation of Metabolism

11.8K

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...

11.8K

01:19

Interactions Between Signaling Pathways

7.4K

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...