食事によるPDGFccの生成はエネルギー貯蔵を制御する
Nehemiah Cox1, Lucile Crozet1,2, Inge R Holtman3
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Science (New York, N.Y.)
|July 2, 2021
まとめ
マクロファージは新しい経路で エネルギー貯蔵を制御します これらの細胞によって生成される血小板由来成長因子 (PDGFcc) は,脂質貯蔵を制御し,代謝障害に対する新しい治療目標を提供します.
科学分野:
- 代謝の調節
- セル・シグナル
- マクロファージの生物学
背景:
- エネルギー貯蔵のマクロファージの調節メカニズムはよく理解されていません.
- 血小板由来成長因子 (PDGF) /血管内皮成長因子 (VEGF) 家族は細胞プロセスに役割を果たします.
- 脂肪細胞の脂質貯蔵はエネルギーホメオスタシスにとって極めて重要です.
研究 の 目的:
- マクロファージがエネルギー貯蔵を制御する新しいメカニズムを特定する.
- 脂質代謝におけるPDGF/VEGFファミリーの役割を調査する.
- 代謝障害に対する潜在的な薬理学的介入を探求する.
主な方法:
- ドロソフィラ幼虫の遺伝子スクリーニングで,主要な調節物質を特定する.
- ネズミのモデルで遺伝子と薬理学的アプローチを利用する.
- 新生児と成人のマウスの脂肪組織におけるPDGFccの役割を調査する.
主要な成果:
- マクロファージによって生成されるPDGF/VEGFファミリーのオートログであるPvf3が特定され,ドロソフィラの脂質貯蔵に不可欠である.
- ネズミのPDGFccは脂肪組織に宿るマクロファージによって生成され,レプチン受容体とCCR2から独立して脂肪細胞の脂質貯蔵を調節することが示された.
- PDGFccの産生は食事によって制御され,パラクリン作用があることが示された.
- PDGFccの阻害により,熱生成のために余分な脂質を茶色脂肪に転向させることが観察された.
結論:
- マクロファージは新しいPDGFcc依存の経路を通じてエネルギー貯蔵を調節する.
- このマクロファージ媒介のメカニズムは,薬理学的介入の潜在的なターゲットを提供します.
- この経路を理解すると 代謝障害とエネルギーバランスの管理のための新しい戦略が生まれます
関連する概念動画
01:58Cell Specific Gene Expression
13.4K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.4K
02:36Cells Coordinate Growth and Proliferation
3.8K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
3.8K
01:15Differentiation of Common Myeloid Progenitor Cells
3.1K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.1K
01:09GPCRs Regulate Adenylyl Cylase Activity
6.9K
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...
6.9K
01:25cAMP-dependent Protein Kinase Pathways
7.3K
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,...
7.3K
01:30Regulation of Food Intake
2.8K
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...
2.8K