DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a β3-adrenoceptor agonist, KTO-7924

Oana, Fumiki; Homma, Toshiki; Takeda, Hiroo; Matsuzawa, Akane; Akahane, Satoshi; Isaji, Masayuki; Akahane, Masuo

doi:10.1016/j.phrs.2005.05.014

Cited by 14 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are also the first to show islet histology after treatment of beta3-adrenergic receptor agonists. We previously reported the upregulation of uncoupling protein 1 (UCP-1) and cytochrome c oxidase subunit VIII-H (COX8H) in the retroperitoneal white adipose tissue of obese (fa/fa) Zucker rats treated with KTO-7924 (15). KTO-7924 also improved lipid metabolism in the rodents.…”

Section: Resultsmentioning

confidence: 99%

“…KTO-7924, whose pharmacological properties have been described elsewhere, was synthesized at Kissei Pharmaceutical Co., Ltd (15)(16)(17). The selectivity of KTO-7924 for the human beta3-adrenergic receptor versus beta-1 and beta-2 is by factors of >53,061 and 265 times, respectively.…”

Section: Preparation Of Kto-7924mentioning

confidence: 99%

“…In the present study, we analyzed the changes in biochemical parameters in obese diabetic C57BL/KsJ-db/db mice treated for 28 days with a newly developed beta3-adrenergic receptor agonist, KTO-7924, which has been reported to ameliorate insulin resistance (15)(16)(17). A close correlation exists between decreased beta3-adrenergic receptor function and energy balance (18), although the mechanism underlying the initiation of diabetes is still under investigation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

KTO-7924, a Beta3-adrenergic Receptor Agonist, Reduces Hyperglycemia, and Protects Beta-cells in the Islets of Langerhans of db/db Mice

et al. 2010

View full text Add to dashboard Cite

Introduction. The effect of beta3-adrenergic receptor agonists on beta cells in the islets of Langerhans is not yet clear. This study examined the beta3-adrenergic receptor agonist on beta cells in the islets of Langerhans. Methods. Obese diabetic C57BL/KsJ-db/db mice were treated with KTO-7924, a newly-developed beta3-adrenergic receptor agonist for 28-day. We analyzed plasma parameters, insulin resistance, and insulin-positive areas among beta-cells in the islets of Langerhans. Results and Conclusion. After a 28-day oral administration period, plasma levels of hemoglobin (Hb) A1c, glucose, triglyceride (TG), and free fatty acid (FFA) were all significantly reduced in KTO-7924 treatment groups compared with controls. Plasma adiponectin levels decreased with age in the control group, but were significantly higher in a treatment group throughout the study period. Furthermore, sequential administration of KTO-7924 led to an improvement in insulin resistance in the OGTT (Oral glucose tolerance test (OGTT)), and an increase in the percentage of insulin-positive areas among beta-cells in the islets of Langerhans compared with controls. This is the first study to show islet histology after treatment of a beta3-adrenergic receptor agonist, and reveals that KTO-7924 reduces hyperglycemia, and protects beta-cells in the islets of Langerhans of db/db mice.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Kto-7924mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

KTO-7924, a Beta3-adrenergic Receptor Agonist, Reduces Hyperglycemia, and Protects Beta-cells in the Islets of Langerhans of db/db Mice

et al. 2010

View full text Add to dashboard Cite

show abstract

“…27,28 Although one might speculate that these two physiological responses to b-adrenergic stimulation are independent of each other, a recent study has demonstrated that the b 3 -adrenergic agonist, CL-316,243, could reduce white-fat pad size and the size of adipocytes only in wildtype but not in UCP1 knockout mice. 29 A DNA microarray study of WAT from obese (fa/fa) Zucker rats treated with the b 3 -adrenoceptor agonist KTO-7924 revealed specifically enhanced mRNA expressions not only of UCP1 but also of COX8H, 30 which is the terminal enzyme of the mitochondrial respiratory chain 31 and likewise highly expressed in BAT. 32 In line with these data, COX8H expression was also drastically increased in 2-OHOA-treated rats.…”

Section: Effect Of C18 Fatty Acids On Body Weight O Vögler Et Almentioning

confidence: 99%

Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

et al. 2007

View full text Add to dashboard Cite

Objective: To investigate the relationship between chemical structure and physiological effect, the efficacy and the molecular mechanisms involved in the reduction of body weight by C18 fatty acids (stearic, elaidic, oleic, linoleic and 2-hydroxyoleic acids (2-OHOA)). Design: Ad libitum fed, lean Wistar Kyoto rats treated orally with up to 600 mg kg À1 of the fatty acids or vehicle every 12 h for 7 days. Besides, starved rats and rats pairfed to the 2-OHOA-treated group served as additional controls under restricted feeding conditions. Measurements: Body weight, food intake, weight of various fat depots, plasma leptin, hypothalamic neuropeptides, uncoupling proteins (UCP) in white (WAT) and brown adipose tissue (BAT) and phosphorylation level of cyclic AMP (cAMP) response element-binding protein (CREB) in WAT. Results: Only treatment with oleic acid and 2-OHOA induced body weight loss (3.3 and 11.4%, respectively) through reduction of adipose fat mass. Food intake in these rats was lower, although hypothalamic neuropeptide and plasma leptin levels indicated a rise in orexigenic status. Rats pairfed to the 2-hydroxyoleic group only lost 6.3% body weight. UCP1 expression and phosphorylation of CREB was drastically increased in WAT, but not BAT of 2-OHOA-treated rats, whereas no UCP1 expression could be detected in WAT of rats treated with oleic acid. Conclusion: Both cis-configured monounsaturated C18 fatty acids (oleic acid and 2-OHOA) reduce body weight, but the introduction of a hydroxyl group in position 2 drastically increases loss of adipose tissue mass. The novel molecular mechanism unique to 2-hydroxyoleic, but not oleic acid, implies induction of UCP1 expression in WAT by the cAMP/PKA pathwaydependent transcription factor CREB, most probably as part of a transdifferentiation process accompanied by enhanced energy expenditure.

show abstract

“…The differences were intrinsic and persisted during in vitro culture and differentiation (Gesta et al, 2006). A beta3-adrenergic receptor agonist, KTO-7924, given orally to obese (fa/fa) Zucker rats, revealed specifically enhanced mRNA expression of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), both reported as being highly expressed in brown adipose tissue (BAT) and part of the uncoupling of oxidative phosphorylation (Oana et al, 2005).…”

Section: Adipose Tissue and Adipocytesmentioning

confidence: 99%

Application of DNA Microarrays in the Study of Human Obesity and Type 2 Diabetes

Sun

2007

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

DNA microarrays have provided medical researchers with a powerful tool to study the mechanisms of complex diseases, including obesity and type 2 diabetes (T2D). The technology has been used to dissect virtually every aspect of the genetic and molecular basis of these two diseases. Gene expression profiling is the major application of DNA microarrays so far. Subcutaneous fat, visceral fat, adipocyte and preadipocyte, muscle, liver, pancreas and specific nuclei in the hypothalamus under normal and disease conditions are used in addressing the profile of gene expression in obesity and T2D. Comparisons of fat depots in humans and animal models - including ob/ob and db/db mice, diet-induced obese mice, fa/fa Zucker rats, gene knockout (plin (-/-), GLUT4 (-/-)) and transgenic mice (GLUT4-Tg) - have been employed in microarray experiments. The effects of various interventions, such as hormonal and drug treatments, exercise, and surgery, have been studied to determine the expression profile of different developmental stages in cells and the effect of treatment on the two diseases. In this review, the application of microarrays in elucidating the role of retinol binding protein 4 as a link between obesity and T2D is discussed. The possible role in obesity of a common genetic variant near the INSIG2 gene and the discovery of the BBS9 gene are also discussed. The problems and challenges are summarized under eight categories and suggestions for the future direction of research in this area are proposed.

show abstract

DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a β3-adrenoceptor agonist, KTO-7924

Cited by 14 publications

References 23 publications

KTO-7924, a Beta3-adrenergic Receptor Agonist, Reduces Hyperglycemia, and Protects Beta-cells in the Islets of Langerhans of db/db Mice

KTO-7924, a Beta3-adrenergic Receptor Agonist, Reduces Hyperglycemia, and Protects Beta-cells in the Islets of Langerhans of db/db Mice

Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

Application of DNA Microarrays in the Study of Human Obesity and Type 2 Diabetes

Contact Info

Product

Resources

About