Molecular cloning of rat uncoupling protein 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats

Hidaka, Shigekazu; Kakuma, Tatsuyuki; Yoshimatsu, Hironobu; Yasunaga, Seikoh; Kurokawa, Mamoru; Sakata, Toshiie

doi:10.1016/s0005-2760(97)00188-4

Cited by 40 publications

(26 citation statements)

References 19 publications

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“…Serum corticosterone concentra- RNA extraction and Northern blot analysis. Total RNA was extracted using the standard acid guanidinium-phenolchloroform method (18). Details of the Northern blot analysis procedure have been described elsewhere (18).…”

Section: Measurement Of Food Consumption Body Weight Circulating Sumentioning

confidence: 99%

“…Total RNA was extracted using the standard acid guanidinium-phenolchloroform method (18). Details of the Northern blot analysis procedure have been described elsewhere (18). Briefly, cDNA probes for mouse CART and AGRP were prepared by RT-PCR by use of the following primers: CART-sense, 5Ј-AAG TCC AGC ACC ATG GAG AG-3Ј; CART-antisense, 5Ј-TCT TCA TTG TGA CCC GCC AC-3Ј; AGRP-sense, 5Ј-CAT GCT GAC TGC AAT GTT GC-3Ј; AGRP-antisense, 5Ј-CTA GGT GCG ACT ACA GAG G-3Ј.…”

Section: Measurement Of Food Consumption Body Weight Circulating Sumentioning

confidence: 99%

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Hyperleptinemia in A^y/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Tsuruta

Yoshimatsu

Hidaka

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Sakata. Hyperleptinemia in A y /a mice upregulates arcuate cocaine-and amphetamine-regulated transcript expression. Am J Physiol Endocrinol Metab 282: E967-E973, 2002; 10.1152/ajpendo.00292.2001.-The effects of leptin on cocaine-and amphetamine-regulated transcript (CART) and agouti-related protein (AGRP) expression in the hypothalamic arcuate nucleus of obese A y /a mice were investigated. CART mRNA expression was upregulated by 41% and AGRP mRNA downregulated by 78% in hyperleptinemic A y /a mice relative to levels in lean a/a mice. The mRNA expression of these neuropeptides in either young nonobese A y /a mice or rats treated with SHU-9119, a synthetic melanocortin-4 receptor (MC4R) antagonist, did not differ significantly from that in the corresponding controls. After a 72-h fast, which decreased the concentration of serum leptin, CART and AGRP mRNA expression decreased and increased, respectively, in A y /a mice. The expression levels of these neuropeptides in leptin-deficient A y /a ob/ob double mutants were comparable to those in a/a ob/ob mice. Leptin thus modulates both CART and AGRP mRNA expression in obese A y /a mice, whereas leptin signals are blocked at the MCR4R level. Taken together, the present findings indicate that differential expression of these neuropeptides in A y /a and ob/ob mice results in dissimilar progression toward obesity. leptin; lethal yellow mice; agouti-related protein; arcuate nucleus LEPTIN HAS BEEN SHOWN TO INDUCE anorectic effects in rodents, at least in part, by signaling through the melanocortin-4 receptor (MC4R) (36). Agouti protein has a potent antagonistic effect on hypothalamic MC4R (7, 30), and rodents become hyperphagic when signaling is interrupted (19,31). Lethal yellow (A y /a) mice display ectopic overexpression of agouti protein in the brain, which results in defective proopiomelanocortin (POMC)/MC4R signaling and, upon maturation, obesity (7,16,30,44). Because these obese mice are both hyperleptinemic and insensitive to exogenous leptin treatment (16, 44), they are thought to be in a "leptin-resistant state." However, it has been reported that the major effects of POMC-and leptin-induced signals on body weight are independent and additive in A y /a ob/ob doubly mutant mice (3). In addition, full leptin responsiveness is restored in A y /a ob/ob mice (3). These findings indicate that defective signaling through MC4R does not necessarily impair leptin action completely. It is quite likely that leptin continues to act, at least in part, on some hypothalamic neuropeptides in A y /a mice.Cocaine-and amphetamine-regulated transcript (CART) was originally identified as a hypothalamic neuropeptide upregulated by cocaine and amphetamine treatment (6). Central administration of CART induces c-fos expression in several hypothalamic nuclei related with feeding control (11,42). Recombinant CART fragments decreased food intake in rodents (1, 29, 42), whereas anti-CART antibodies increased it (24). Asnicar et al. (2) have recently demonstrated that absence of CART results i...

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Section: Measurement Of Food Consumption Body Weight Circulating Sumentioning

confidence: 99%

Section: Measurement Of Food Consumption Body Weight Circulating Sumentioning

confidence: 99%

Hyperleptinemia in A^y/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Tsuruta

Yoshimatsu

Hidaka

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…As noted above, UCP2 expression in skeletal muscle of human diabetic patients is increased [97,100]. In fa/fa rat muscle, no difference [144] or a decrease in expression is reported [89]. In contrast, non-obese rats made diabetic by streptozotocin injection initially have increased UCP2 in both WAT and skeletal muscle.…”

Section: Relation Of Ucp2 With Metabolic Diseasesmentioning

confidence: 82%

“…Since leptin appears to upregulate UCP2 [42,74], it might be hypothesized that leptin-deficient or leptin-resistant animals would have attenuated UCP2 expression. However, not only is leptin not essential for UCP2 expression, it seems that even similar causes of obesity have disparate effects on UCP2 expression [9,16,89,144]. Moreover, expression of UCP2 in skeletal muscle of these rodents has rarely been reported.…”

Section: Relation Of Ucp2 With Metabolic Diseasesmentioning

confidence: 99%

Uncoupling protein-2: evidence for its function as a metabolic regulator

2002

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Uncoupling protein-2 (UCP2) was discovered in 1997 but a definitive understanding of its functions has so far eluded investigators. Potential roles include regulating fat metabolism directly and indirectly via effects on insulin secretion. Also, UCP2 could also negatively modulate the production of reactive oxygen species (ROS). Although evidence in support of these functions is correlational, research on UCP2 mechanisms of action has recently been published. Studies of polymorphisms in the uncoupling protein-2 gene have not been included in detail here but are reviewed elsewhere [1,2]. For an in depth discussion of the uncoupling protein family of proteins, readers are referred to recent reviews [1, 3]. Chemical properties of uncoupling proteinsMitochondrial metabolism generates more than 90 % of the ATP required by organisms for routine cellular processes. The efficiency of ATP formation could be altered by demand, by drugs or by pathological processes. Uncoupling agents dissociate fuel oxidation in the electron transport chain of mitochondria from phosphorylation of substrate, namely ADP. Normally, glucose-derived NADH and FADH 2 stimulate Diabetologia (2002) AbstractUncoupling protein-2, discovered in 1997, belongs to a family of inner mitochondrial membrane proteins that, in general, function as carriers. The function(s) of uncoupling protein-2 have not yet been definitively described. However, mounting evidence suggests that uncoupling protein-2 could act in multiple tissues as a regulator of lipid metabolism. A role as a modulator of reactive oxygen species as a defence against infection is also postulated. In this review, a brief overview of the general and specific properties of uncoupling protein-2 is given and evidence for metabolic and immune regulatory functions is summarized.Uncoupling protein-2 could have particular importance in the regulation of lipid metabolism in adipose tissue and skeletal muscle. In addition, its ability to inhibit insulin secretion could also promote fat utilization over storage. Inhibition by uncoupling protein-2 of reactive oxygen species formation in macrophages and other tissues could have implications for regulation of immune function. The possibility of functions of uncoupling protein-2 in other tissues such as the brain are beginning to emerge. [Diabetologia (2002) 45: 174±187]

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“…Uncoupling protein-2 exhibits 59%, 71%, 33%, and 38% structural similarities with UCP1, -3, -4, and -5, respectively (Fleury and Sanchis, 1999;Vidal-Puig et al, 1997). The rat UCP2 shares approximately 99% and 95% sequence homology with the UCP2 of the mouse and human, respectively, which emphasizes the remarkable conservation of UCP2 (Hidaka et al, 1998).…”

Section: Structure and Action Of Uncoupling Protein-2mentioning

confidence: 89%

Neuroprotective Role of Mitochondrial Uncoupling Protein 2 in Cerebral Stroke

Mehta

2009

J Cereb Blood Flow Metab

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The uncoupling proteins (UCPs) are mitochondrial transporter proteins involved in proton conductance across inner mitochondrial membrane (IMM). UCP2, which is one of the members of this class of proteins, has a wide but restricted tissue distribution including brain. Its physiologic role according to emerging evidences, although still not clear, indicate that distribution of UCP2 may be related to regulation of mitochondria membrane potential (DWm), production of reactive oxygen species (ROS), preservation of calcium homeostasis, modulation of neuronal activity, and eventually inhibition of cellular damage. These factors are very important in determining the fate of neurons and damage progression in the brain during various neurodegenerative diseases including cerebral stroke. Recent evidence indicates that an increased expression and activity of UCP2 are well correlated with neuronal survival after stroke and trauma. This review briefly covers the present understanding of UCP2, which eventually may be beneficial to understand the precise role of UCP2 to develop strategy to identify its potential therapeutic application.

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Molecular cloning of rat uncoupling protein 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats

Cited by 40 publications

References 19 publications

Hyperleptinemia in A^y/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Hyperleptinemia in A^y/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Uncoupling protein-2: evidence for its function as a metabolic regulator

Neuroprotective Role of Mitochondrial Uncoupling Protein 2 in Cerebral Stroke

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Molecular cloning of rat uncoupling protein 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats

Cited by 40 publications

References 19 publications

Hyperleptinemia in Ay/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Hyperleptinemia in Ay/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Uncoupling protein-2: evidence for its function as a metabolic regulator

Neuroprotective Role of Mitochondrial Uncoupling Protein 2 in Cerebral Stroke

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Product

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Hyperleptinemia in A^y/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression

Hyperleptinemia in A^y/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression