Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice
Joachim Fruebis,Tsu-Shuen Tsao,Sandrine Javorschi,Dana Ebbets-Reed,Mary Ruth Erickson,Frances T. Yen,Bernard Bihain,Harvey F. Lodish +7 more
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TLDR
Daily administration of a very low dose of gAcrp30 to mice consuming a high-fat/sucrose diet caused profound and sustainable weight reduction without affecting food intake.Abstract:
Adipocyte complement-related protein (30 kDa) (Acrp30), a secreted protein of unknown function, is exclusively expressed in differentiated adipocytes; its mRNA is decreased in obese humans and mice. Here we describe novel pharmacological properties of the protease-generated globular head domain of Acrp30 (gAcrp30). Acute treatment of mice with gAcrp30 significantly decreased the elevated levels of plasma free fatty acids caused either by administration of a high fat test meal or by i.v. injection of Intralipid. This effect of gAcrp30 was caused, at least in part, by an acute increase in fatty acid oxidation by muscle. As a result, daily administration of a very low dose of gAcrp30 to mice consuming a high-fat/sucrose diet caused profound and sustainable weight reduction without affecting food intake. Thus, gAcrp30 is a novel pharmacological compound that controls energy homeostasis and exerts its effect primarily at the peripheral level.read more
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Insulin signalling and the regulation of glucose and lipid metabolism
Alan R. Saltiel,C. Ronald Kahn +1 more
TL;DR: The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide, and tissues such as muscle, fat and liver become less responsive or resistant to insulin.
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The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Toshimasa Yamauchi,Junji Kamon,Hironori Waki,Yasuo Terauchi,Naoto Kubota,Kazuo Hara,Y. Mori,Tomohiro Ide,Kouji Murakami,Nobuyo Tsuboyama-Kasaoka,Osamu Ezaki,Y. Akanuma,Oksana Gavrilova,Charles Vinson,Marc L. Reitman,Hiroyuki Kagechika,Koichi Shudo,Madoka Yoda,Yasuko Nakano,Kazuyuki Tobe,R. Nagai,Shigeko Kimura,Motowo Tomita,Philippe Froguel,Takashi Kadowaki +24 more
TL;DR: It is concluded that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy and that the replenishment of adiponECTin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
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Increased oxidative stress in obesity and its impact on metabolic syndrome
Shigetada Furukawa,Takuya Fujita,Michio Shimabukuro,Masanori Iwaki,Yukio Yamada,Yoshimitsu Nakajima,Osamu Nakayama,Makoto Makishima,Morihiro Matsuda,Iichiro Shimomura +9 more
TL;DR: It is suggested that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.
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Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
Toshimasa Yamauchi,Junji Kamon,Yasuhiko Minokoshi,Yoichi M. Ito,Hironori Waki,S. Uchida,Shigeo Yamashita,Mitsuhiko Noda,Shunbun Kita,K Ueki,Koji Eto,Y. Akanuma,Philippe Froguel,Fabienne Foufelle,Pascal Ferré,David Carling,Shigeko Kimura,Ryozo Nagai,Barbara B. Kahn,Takashi Kadowaki +19 more
TL;DR: It is shown that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full- lengths Ad in the liver, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.
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Adipokines in inflammation and metabolic disease
TL;DR: The role of adipokines in inflammatory responses is focused on and their potential as regulators of metabolic function is discussed.
References
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A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
TL;DR: A novel 30-kDa secretory protein, Acrp30 (adipocyte complement-related protein of 30 kDa), that is made exclusively in adipocytes and whose mRNA is induced over 100-fold during adipocyte differentiation is described.
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Gökhan S. Hotamisligil,Pascal Peraldi,Adriane I. Budavari,Ramsey Ellis,Morris F. White,Bruce M. Spiegelman +5 more
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AdipoQ is a novel adipose-specific gene dysregulated in obesity.
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Kazuhisa Maeda,Kousaku Okubo,Iichiro Shimomura,Tohru Funahashi,Yuji Matsuzawa,Kenichi Matsubara +5 more
TL;DR: The apM1 gene encodes a 244 amino acid open reading frame containing a putative signal sequence and G-X-Y repeats (66 amino acids) followed by a cluster of aromatic residues near the C terminus having high local similarity with collagens X and VIII and complement factor C1q.
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