関連する実験動画

Updated: Dec 20, 2025

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide

Published on: May 12, 2023

肝臓のNADH還元性ストレスは,代謝特性の一般的な変化の基礎となっている

Russell P Goodman^1,2, Andrew L Markhard¹, Hardik Shah¹

¹Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.

|May 29, 2020

まとめ

バクテリアの酵素を用いてマウスの細胞内NADH/NAD+比を低下させると,アルファ-ヒドロキシブチラートが還元性ストレスマーカーであることを明らかにした. インスリン抵抗性などの代謝疾患に遺伝的変異を因果的に結びつけています

科学分野:

生物化学
代謝生理学
ミトコンドリア生物学

背景:

細胞内のNADH/NAD+比は生化学において極めて重要であるが,生体内の代謝生理学におけるその役割は不明である.
還元性ストレスと呼ばれる肝細胞性NADH/NAD+比の上昇は,代謝機能障害と関連しています.
アルファ・ヒドロキシブチラートの循環は,ヒトにおけるグルコース耐性障害,インスリン抵抗性,ミトコンドリア疾患と関連している.

研究の目的:

肝細胞 NADH/NAD+ の比率を直接低下させる in vivo 代謝の結果を調査する.
還元性ストレスを評価するために,新しい遺伝子ツールであるLactobacillus brevis (Lb) NOXを使用します.
代謝特性の遺伝的変異の影響を媒介するNADH還元性ストレスの因果的役割を調査する.

主な方法:

ラクトバシルス・ブレヴィス (Lb) NOX,バクテリアの水形成NADH酸化酵素をマウスにインビボで適用する.
メタボロミクスを遺伝子ツールと統合して,代謝変化を分析する.
循環中の代謝産物,グルコース耐性,ホルモンレベル (例えばFGF21) の評価

主要な成果:

循環中のアルファ・ヒドロキシブチレートのレベルは,肝細胞 NADH/ NAD+ の比率上昇 (減少性ストレス) の強力なマーカーとして特定されました.
LbNOXの適用は,NADHの還元ストレスが代謝特性に対するGCKR遺伝的変異の影響を因果的に媒介することを示した.
主な代謝特性には,循環するトリグリセリドレベル,グルコース耐性,FGF21レベルが含まれます.

結論:

肝臓のNADH/NAD+比が上昇することは,ヒトの遺伝的変異によって影響される重要な代謝パラメータである.
インスリン抵抗性や脂質不全を含む主要な代謝特性や疾患において,NADH還元ストレスが因果的な役割を果たします.
LbNOXのような遺伝的ツールは"因果代謝"を研究し,代謝疾患のメカニズムを理解するために価値があります.

さらに関連する動画

Measurements of Physiological Stress Responses in C. Elegans

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes

An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes

Published on: April 26, 2019

関連する概念動画

Role of Reduced Coenzymes NADH and FADH₂

Role of Reduced Coenzymes NADH and FADH₂

The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...

Regulation of Metabolism

Regulation of Metabolism

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...

Human Genetics

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...

Redox Reactions

Redox Reactions

Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...

Overview of Lipid Metabolism

Overview of Lipid Metabolism

Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...

Metabolic States of the Body: Fasting and Starvation

Metabolic States of the Body: Fasting and Starvation

During the initial hours of fasting, the body uses up its glycogen stores as an energy source. Once these glycogen reserves are depleted, the body begins breaking down stored triglycerides and structural proteins. During this stage, glycerol becomes a key substrate for gluconeogenesis, while free fatty acids undergo beta-oxidation to provide energy for tissues, such as skeletal muscle. In the fasting state, the body spares protein breakdown as much as possible to conserve muscle and structural...