Uncoupling proteins 2 and 3 are highly active H
            <sup>+</sup>
            transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)

Echtay, Karim S.; Winkler, Edith; Frischmuth, Karina; Klingenberg, Martin

doi:10.1073/pnas.98.4.1416

Cited by 308 publications

(268 citation statements)

References 54 publications

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“…Because UCP3 is expressed primarily in skeletal muscle, the major tissue mass in most vertebrates, up-regulation of UCP3 may be responsible at least in part for the C75-induced increase in energy expenditure. Fatty acids are needed to fuel this thermogenic response (32). Closely correlated to the upregulation of UCP3, induced by centrally administered C75, is an increase of fatty acid oxidation by skeletal muscle (8) and in C2C12 muscle cells in culture (Fig.…”

Section: Effect Of Ectopically Expressed Pgc-1␣ On Fatty Acid Oxidatimentioning

confidence: 99%

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α

Hun¹,

Rodgers

Puigserver

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Previous investigations show that intracerebroventricular administration of a potent inhibitor of fatty acid synthase, C75, increases the level of its substrate, malonyl-CoA, in the hypothalamus. The ''malonyl-CoA signal'' is rapidly transmitted to skeletal muscle by the sympathetic nervous system, increasing fatty acid oxidation, uncoupling protein-3 (UCP3) expression, and thus, energy expenditure. Here, we show that intracerebroventricular or intraperitoneal administration of C75 increases the number of mitochondria in white and red (soleus) skeletal muscle. Consistent with signal transmission from the hypothalamus by the sympathetic nervous system, centrally administered C75 rapidly (<2 h) up-regulated the expression (in skeletal muscle) of the ␤-adrenergic signaling molecules, i.e., norepinephrine, ␤3-adrenergic receptor, and cAMP; the transcriptional regulators peroxisomal proliferator activator regulator ␥ coactivator 1␣ (PGC-1␣) and estrogen receptor-related receptor ␣ (ERR␣); and the expression of key oxidative mitochondrial enzymes, including pyruvate dehydrogenase kinase, mediumchain length fatty acyl-CoA dehydrogenase, ubiquinone-cytochrome c reductase, cytochrome oxidase, as well as ATP synthase and UCP3. The role of PGC-1␣ in mediating these responses in muscle was assessed with C2C12 myocytes in cell culture. Consistent with the in vivo response, adenovirus-directed expression of PGC-1␣ in C2C12 muscle cells provoked the phosphorylation͞ inactivation and reduced expression of acetyl-CoA carboxylase 2, causing a reduction of the malonyl-CoA concentration. These effects, coupled with an increased carnitine palmitoyltransferase 1b, led to increased fatty acid oxidation. PGC-1␣ also increased the expression of ERR␣, PPAR␣, and enzymes that support mitochondrial fatty acid oxidation, ATP synthesis, and thermogenesis, apparently mediated by an increased expression of UCP3. C75 ͉ energy expenditure ͉ sympathetic nervous system ͉ uncoupling protein 3 ͉ C2C12 myocytes T he level of hypothalamic malonyl-CoA, an intermediate in the pathway of de novo fatty acid synthesis, is an indicator of whole-body energy status (1-5). The malonyl-CoA concentration responds to changes in energy balance by signaling to higher brain centers that regulate feeding behavior and to peripheral tissues that alter energy expenditure (1). Hypothalamic malonylCoA is also responsive to centrally administered inhibitors of fatty acid synthesis (4) and to the ectopic expression of malonylCoA decarboxylase in the ventral hypothalamus (5, 6). The malonyl-CoA signal is rapidly relayed by the sympathetic nervous system (SNS) to skeletal muscle, where energy expenditure is up-regulated through increased fatty acid oxidation and thermogenic uncoupling mediated by uncoupling protein 3 (UCP3) (7,8). Thus, a regulatory linkage exists between the anabolic pathway of fatty acid synthesis in the hypothalamus and food intake and energy expenditure.A substantial body of evidence indicates that malonyl-CoA acts as a signaling intermediary in this regu...

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Section: Effect Of Ectopically Expressed Pgc-1␣ On Fatty Acid Oxidatimentioning

confidence: 99%

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α

Hun¹,

Rodgers

Puigserver

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, BBR increased the expression of uncoupling protein 2 (UCP2; Fig. 4A), which is thought to be associated with energy expenditure by dissipating the chemiosmotic gradient in mitochondria (10,11,28).…”

Section: Bbr Alleviates Dyslipidemia and Fatty Liver In Obese Micementioning

confidence: 99%

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

Kim

Lee

Hun

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

208

146

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AMP-activated protein kinase (AMPK) plays an important role in regulating whole body energy homeostasis. Recently, it has been demonstrated that berberine (BBR) exerts antiobesity and antidiabetic effects in obese and diabetic rodent models through the activation of AMPK in peripheral tissues. Here we show that BBR improves lipid dysregulation and fatty liver in obese mice through central and peripheral actions. In obese db/db and ob/ob mice, BBR treatment reduced liver weight, hepatic and plasma triglyceride, and cholesterol contents. In the liver and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and changed expression of genes involved in lipid metabolism. Additionally, intracerebroventricular administration of BBR decreased the level of malonyl-CoA and stimulated the expression of fatty acid oxidation genes in skeletal muscle. Together, these data suggest that BBR would improve fatty liver in obese subjects, which is probably mediated not only by peripheral AMPK activation but also by neural signaling from the central nervous system.

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“…15 -18 UCP2 and UCP3 have been shown by the group of Klingenberg to function as real uncoupling proteins, similarly to UCP1. 19 Their expression in many mammalian tissues (brown fat, skeletal muscle, heart, kidney, lung, placenta, lymphocytes and white fat) 8 may suggest that the metabolic changes in obesity may also concern other tissues, whose importance for the whole metabolic turnover is not high. Among them also belong the lymphocytes from peripheral blood, which represent easily available cells for the study of mitochondrial energy providing systems.…”

Section: Introductionmentioning

confidence: 99%

Activities of cytochrome c oxidase and citrate synthase in lymphocytes of obese and normal-weight subjects

et al. 2002

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BACKGROUND: Obesity represents a heterogeneous group of disorders associated with broad spectrum of metabolic and endocrine abnormalities. The metabolic changes in obesity may also concern the efficacy of mitochondrial system of energy provision. The aim of our study was to analyse activities of mitochondrial enzymes cytochrome c oxidase (COX) and citrate synthase (CS) in isolated lymphocytes of obese and normal-weight subjects. RESULTS: In the group of 304 non-obese controls, differences between men and women were found neither in the COX and CS activities nor in the COX=CS ratio in isolated lymphocytes. The activity of COX did not change even with age, whereas the activity of CS decreased significantly resulting in age-dependent increase of the COX=CS ratio (P < 0.01). In the group of 60 obese patients aged 17 -75 y, the COX activity was 1.2-fold higher (P < 0.01) and the CS activity was 1.3-fold lower (P < 0.01) compared to 151 non-obese healthy age-matched controls. Consequently, the COX=CS ratio became 1.7-fold higher (P < 0.01) in the obese patients compared to the non-obese population, which indicates that both the absolute and relative oxidative capacity are increased. CONCLUSION: Isolated lymphocytes from peripheral blood contribute very little to the overall metabolic turnover, but they may serve as easily available marker cells for studying the changes of mitochondrial energy converting systems in obesity.

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Uncoupling proteins 2 and 3 are highly active H ⁺ transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)

Cited by 308 publications

References 54 publications

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

Activities of cytochrome c oxidase and citrate synthase in lymphocytes of obese and normal-weight subjects

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Uncoupling proteins 2 and 3 are highly active H + transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)

Cited by 308 publications

References 54 publications

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

Activities of cytochrome c oxidase and citrate synthase in lymphocytes of obese and normal-weight subjects

Contact Info

Product

Resources

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Uncoupling proteins 2 and 3 are highly active H ⁺ transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)