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en: Cold-induced changes in gene expression in brown adipose tissue: implications for the activation of thermogenesis.

en: Brown adipose tissue (BAT) is the site of heat production (thermogenesis). This unique function is performed by uncoupling protein 1 (UCP1) specifically expressed in mitochondria of BAT. UCP1 dissipates the driving force of ATP synthesis, and thus causes heat production followed by energy expenditure. The thermogenic function of BAT has the role of maintaining body temperature under cold conditions. When animals are exposed to cold, the expression of UCP1 gene is increased to activate thermogenesis. To date, functional analysis of BAT has been focused on UCP1, because it plays an indispensable role in thermogenesis. However, the gene expression of not only UCP1 but also that of other genes in BAT is expected to be regulated to achieve effective thermogenesis. Our previous investigations showed increased expression of genes that encode several energy metabolic enzymes in the BAT of rats kept in the cold. These changes in gene expression imply that the enhancement of energy metabolism is needed to activate thermogenesis. Furthermore, various reports from studies focused on genes whose expression is changed in response to cold stimulation have provided new insights into the function of BAT. In this review, to understand the thermogenic function of BAT systematically, we have provided an overview of previous findings on changes in the expression of genes thought to be related to the activation of thermogenesis in BAT.

en: Biological & Pharmaceutical Bulletin

ja: Biological & Pharmaceutical Bulletin


en: Exploratory Studies on Biomarkers : An Example Study on Brown Adipose Tissue

ja: バイオマーカーの探索:褐色脂肪組織に関する研究事例

en: In mammals, two kinds of adipose tissue are known to exist, i.e., white (WAT) and brown (BAT) adipose tissue. The physiological role of WAT is storage of excess energy as fat, whereas that of BAT is the expenditure of excess energy as heat. The uncoupling protein UCP1, which is specifically expressed in brown fat mitochondria, dissipates the proton electrochemical potential across the inner mitochondrial membrane, known as a driving force of ATP synthesis, and thus it dissipates excess energy in a form of heat. Because deficiency in effective expenditure of excess energy causes accumulation of this energy in the form of fat (i.e., obesity), it is very important to understand the energy metabolism in this tissue for the development of anti-obesity drugs. In this article, in addition to providing a brief introduction to the functional properties of BAT and UCP1, the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

en: IEEJ Transactions on Electronics, Information and Systems

ja: 電気学会論文誌C (電子，情報，システム部門誌)


en: Identification of muscle-type carnitine palmitoyltransferase I and characterization of its gene structure

ja: 筋型カルニチンパルミトイル転移酵素の発見とその遺伝子構造の解析

en: To characterize energy metabolism in brown adipose tissue (BAT), differential screening of a cDNA library of rat BAT with a cDNA probe of rat white adipose tissue was carried out. We isolated one novel cDNA clone encoding a protein of 88.2 kDa consisting of 772 amino acids. The deduced amino acid sequence showed the highest homology (62.6%) with that of rat liver carnitine palmitoyltransferase I (CPTI). The transcript corresponding to this cDNA was abundantly expressed not only in BAT but also in the heart and skeletal muscle. CPTI is a protein necessary for the beta-oxidation of long-chain fatty acids in mammalian mitochondria, and it has been suggested that at least two isoforms, the liver type and muscle (M-CPTI) type, exist. Based on these observations, we concluded that the novel cDNA clone isolated from rat BAT encodes M-CPTI. Isolation and characterization of a genomic DNA clone revealed that the gene for human M-CPTI consists of two 5'-noncoding exons, 18 coding exons, and one 3'-noncoding exon spanning approximately 10 kbp, and a gene encoding choline/ethanolamine kinase-beta (CK/EK-beta) was located about 300 bp upstream from the M-CPTI gene with the same strand direction. Furthermore, we found atypical transcripts containing exons of both CK/EK-beta and M-CPTI genes in humans and rodents. The physiologic role(s) of these transcripts is still unknown. However, it is interesting that such transcripts are produced from two tightly arranged and functionally unrelated genes in mammalian tissues.

en: Journal of the Pharmaceutical Society of Japan

ja: 薬学雑誌


en: Identification of Muscle-Type Carnitine Palmitoyltransferase I and Characterization of Its Atypical Gene Structure

en: To characterize energy metabolism in rat brown adipose tissue (BAT), we carried out differential screening of a cDNA library of BAT with a cDNA probe of white adipose tissue and isolated one novel cDNA clone. It contained a single open-reading frame of 2316 bases, which encodes a protein of 88.2 kDa. The predicted amino acid sequence showed the highest homology (62.6%) with that of carnitine palmitoyltransferase I (CPTI) from rat liver. The transcript corresponding to this cDNA was found to be abundantly expressed not only in BAT but also in heart and skeletal muscle. CPTI is known to be a protein necessary for the beta-oxidation of long-chain fatty acids in mammalian mitochondria, and it has been suggested that at least two isoforms, the liver type and muscle type, exist. From these observations, a cDNA clone isolated from rat BAT was concluded to be encoding muscle-type CPTI (M-CPTI). Characterization of a genomic DNA clone revealed that the gene for human M-CPTI consists of two 5'-noncoding exons, 18 coding exons, and one 3'-noncoding exon spanning approximately 10 kbp, and a gene encoding choline/ethanolamine kinase-beta (CK/EK-beta) was located only about 300 bp upstream from the M-CPTI gene with the same strand direction. Furthermore, we found that unordinary transcripts containing exons of both CK/EK-beta and M-CPTI genes exist in human and rodent tissues. Although the physiologic role(s) of these transcripts is still unknown, it is interesting that such transcripts are produced from two tightly arranged and functionally unrelated genes.


en: Identification of possible protein machinery involved in the thermogenic function of brown adipose tissue.

en: Brown adipose tissue (BAT) is believed to function by dissipating excess energy in mammals. It is very important to understand the energy metabolism held in BAT since disorder of its energy-dissipating function may cause obesity or lifestyle-related diseases such as hypertension and diabetes. This function in BAT is mainly attributable to uncoupling protein (UCP), specifically expressed in its mitochondria. This protein consumes excess energy as heat by dissipating the H+ gradient across the inner mitochondrial membrane that is utilized as a driving force for ATP synthesis. In this review article, in addition to providing a brief introduction to the functional properties of BAT and UCP, we also describe and discuss properties of cultured brown adipocytes and the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

en: The Journal of Medical Investigation : JMI


en: Bioenergetics in brown adipose tissue.

ja: Bioenergetics in brown adipose tissue.

en: Recent Res. Devel.Bioener.

ja: Recent Res. Devel.Bioener.


en: ミトコンドリア輸送タンパクスーパーファミリー

ja: ミトコンドリア輸送タンパクスーパーファミリー

en: 生体の科学

ja: 生体の科学