{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:23:09Z","timestamp":1791094989717,"version":"4.1.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,4,1]]},"abstract":"<jats:p>AMP-activated protein kinase (AMPK) is a key regulator of glucose and fatty acid homeostasis. In muscle cells, AMPK stimulates mitochondrial fatty acid oxidation and ATP production. The thyroid hormone T3 increases cellular oxygen consumption and is considered to be a major regulator of mitochondrial activities. In this study, we examined the possible involvement of AMPK in the stimulatory action of T3 on mitochondria. Treatment of C2C12 myoblasts with T3 rapidly led to phosphorylation of AMPK. Acetyl-coenzyme A carboxylase, a direct target of AMPK, was also phosphorylated after T3 treatment. Similar results were obtained with 3T3-L1, FRTL-5, and HeLa cells. Stable expression of T3 receptor (TR)-\u03b1 or TR\u03b2 in Neuro2a cells enhanced this effect of T3, indicating the involvement of TRs. Because HeLa cells express only Ca2+\/calmodulin-dependent protein kinase kinase-\u03b2 (CaMKK\u03b2), one of two known AMPK kinases, it was suggested that the effect of T3 is mediated by CaMKK\u03b2. Indeed, experiments using a CaMKK inhibitor, STO-609, and an isoform-specific small interfering RNA demonstrated the CaMKK\u03b2-dependent phosphorylation of AMPK. Furthermore, T3 was found to rapidly induce intracellular Ca2+ mobilization in HeLa cells, and a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N\u2032,N\u2032-tetraacetic acid (BAPTA), suppressed T3- as well as ionomycin-dependent phosphorylation of AMPK. In addition, T3-dependent oxidation of palmitic acids was attenuated by BAPTA, STO-609, and the small interfering RNA for CaMKK\u03b2, indicating that T3-induced activation of AMPK leads to increased fatty acid oxidation. These results demonstrate that T3 nontranscriptionally activates AMPK via intracellular Ca2+ mobilization and CaMKK\u03b2 activation, thereby stimulating mitochondrial fatty acid oxidation.<\/jats:p>","DOI":"10.1210\/me.2007-0249","type":"journal-article","created":{"date-parts":[[2008,1,11]],"date-time":"2008-01-11T01:58:41Z","timestamp":1200016721000},"page":"893-903","source":"Crossref","is-referenced-by-count":53,"title":["Thyroid Hormone Activates Adenosine 5\u2032-Monophosphate-Activated Protein Kinase via Intracellular Calcium Mobilization and Activation of Calcium\/Calmodulin-Dependent Protein Kinase Kinase-\u03b2"],"prefix":"10.1210","volume":"22","author":[{"given":"Masako","family":"Yamauchi","sequence":"first","affiliation":[{"name":"Department of Endocrinology (M.Y., F.K., X.C., X.L., Y.K., H.S.), Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan"},{"name":"Department of Endocrinology and Diabetes (M.Y., Y.O.), Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukushi","family":"Kambe","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (M.Y., F.K., X.C., X.L., Y.K., H.S.), Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (M.Y., F.K., X.C., X.L., Y.K., H.S.), Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (M.Y., F.K., X.C., X.L., Y.K., H.S.), Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Kozaki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (M.Y., F.K., X.C., X.L., Y.K., H.S.), Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Oiso","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes (M.Y., Y.O.), Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (M.Y., F.K., X.C., X.L., Y.K., H.S.), Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614071267700_R1","first-page":"48","article-title":"AMPK: a key sensor of fuel and energy status in skeletal muscle.","volume":"21","author":"Hardie","year":"2006","journal-title":"Physiology (Bethesda)"},{"key":"2020071614071267700_R2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cmet.2004.12.003","article-title":"AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism.","volume":"1","author":"Kahn","year":"2005","journal-title":"Cell Metab"},{"key":"2020071614071267700_R3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ceb.2005.01.006","article-title":"New roles for the LKB1\u2192AMPK pathway.","volume":"17","author":"Hardie","year":"2005","journal-title":"Curr Opin Cell 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