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1.
Sci Rep ; 12(1): 3555, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241766

RESUMO

Kadaknath, the only black chicken indigenous to India, faces the threat of extinction due to declining numbers. Its meat is used in tribal medicine for invigorating and health-promoting properties. Expectations of immune-boosting and therapeutic properties in its meat are creating a buzz these days. Thus, Kadaknath meat was explored and further compared with the commercial Cobb 400 broiler (Cobb) for the functional traits that might be contributing towards proclaimed pharmacological benefits. Birds (n = 20/ group) were raised under similar management conditions and the two primal chicken meat cuts (breast and thigh) were collected at the marketing age. Kadaknath meat was found to be an enriched source of functional biomolecules (carnosine, anserine, creatine). Its breast meat carnosine content was more than double of the Cobb broiler, 6.10 ± 0.13 and 2.73 ± 0.1 mg/ g of wet tissue, respectively. Similarly, the thigh meat of Kadaknath was a significantly (P < 0.05) richer source of carnosine. The genetic background was a key determinant for muscle carnosine content as a significant abundance of CARNS1 and SLC36A1 expression was identified in the Kadaknath breast. The superior functional property of Kadaknath meat was established by the antioxidant capacity established by the Oxygen radical absorbance capacity assay and a stronger ability to inhibit the formation of advanced glycation end products (AGEs). The identification of fairly unknown nutritional and functional advantages of Kadaknath meat could potentially change the paradigm with its meat consumption. It will help in developing a brand name for Kadaknath products that will propel an increase in its market share and ultimately conservation of this unique but endangered poultry germplasm.


Assuntos
Carnosina , Galinhas , Animais , Anserina/metabolismo , Carnosina/metabolismo , Galinhas/genética , Carne/análise , Aves Domésticas
2.
Eur J Pharmacol ; 727: 1-7, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24486398

RESUMO

GPR81, which exhibits a high degree of homology with GPR109a, has been recently identified as a lactate receptor. Similar to GPR109a, the activation of GPR81 by lactate suppresses lipolysis, suggesting that GPR81 may be a potential drug target for treating dyslipidemia. In addition, the fact that GPR81 is expressed only in adipocytes, whereas GPR109a is expressed in various tissues and cells, including Langerhans cells, which are considered responsible for flushing, indicates that targeting GPR81 could lead to the development of antidyslipidemia agents with a reduced risk of this side effect. However, the pharmacological role of GPR81 remains largely unclear, mainly because of the lack of potent and selective surrogate GPR81 agonists suitable for in vivo studies. In the present study, we showed that lactate-induced suppression of lipolysis in explants of white adipose tissue (WAT) depends on the presence of GPR81. We also performed high-throughput screening (HTS) and identified four novel chemical clusters as GPR81 agonists. Chemical optimization of aminothiazole derivatives led to the discovery of a lead compound with improved potency. The compound inhibited lipolysis in differentiated 3T3-L1 adipocytes. Finally, intraperitoneal administration of this compound suppressed lipolysis in mice at doses that did not cause cutaneous flushing. This is the first description of a 50nM GPR81 selective agonist with in vivo efficacy, without the side effect, i.e., flushing. These results suggest that GPR81 is an attractive drug target for treating dyslipidemia without the risk of flushing.


Assuntos
Adipócitos/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Rubor/prevenção & controle , Hipolipemiantes/farmacologia , Lipólise/efeitos dos fármacos , Receptores Acoplados a Proteínas G/agonistas , Tiazóis/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Relação Dose-Resposta a Droga , Descoberta de Drogas , Ensaios de Triagem em Larga Escala , Hipolipemiantes/administração & dosagem , Hipolipemiantes/síntese química , Injeções Intraperitoneais , Ácido Láctico/farmacologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-Atividade , Tiazóis/administração & dosagem , Tiazóis/síntese química , Transfecção
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