Effect of tetra-hydroxylated bile acid on size and insulin sensitivity of subcutaneous adipocytes in healthy lean cats

IF 1.9 2区 农林科学 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE
I.T. Rast , E. Zini , C. Wolfrum , T.A. Lutz , C.E. Reusch , E. Salesov
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引用次数: 0

Abstract

Obesity leads to insulin resistance and is a major risk factor for the development of diabetes mellitus in cats. Prevention of obesity and obesity-induced insulin resistance is difficult, and reliable long-term strategies are currently lacking. Retinoid-related orphan receptor gamma (RORγ) was recently identified as an important transcription factor in the development of large insulin-resistant adipocytes in mice and humans. RORγ negatively affects adipocyte differentiation through expression of its target gene matrix metalloproteinase 3 (MMP3) and promotes the development of large insulin-resistant adipocytes. Preliminary studies in mice showed that RORγ can be inhibited by its ligand tetra-hydroxylated bile acid (THBA). In the present study, serum THBA levels were determined in healthy and diabetic cats. Moreover, potential side effects and the effects of THBA supplementation on adipocyte size, mRNA expression of RORγ, MMP3, interleukin 6, tumor necrosis factor α, adiponectin and leptin in feline subcutaneous adipocytes and insulin sensitivity were investigated in healthy normal weight cats. Thirteen healthy and 13 diabetic cats were used for determination of serum THBA level, and six healthy normal-weight cats were included in a feeding trial. Similar THBA levels were determined in serum of healthy and diabetic cats. Supplementation of 5 mg/kg THBA for 8 wk did not cause any negative effect on feeding behavior, general condition and blood parameters of tested cats. It significantly reduced adipocyte size and mRNA expression of MMP3, interleukin 6, and tumor necrosis factor α in adipocytes, while mRNA expression of adiponectin significantly increased and mRNA expression of RORγ and leptin remained unchanged. Administration of THBA did not influence fasting blood glucose levels or the response of cats to acute insulin administration. Based on these results, THBA is palatable and is considered safe for use in cats. It reduces expression of MMP3 and promotes the development of small adipocytes with increased expression of adiponectin and reduced expression of interleukin 6 and tumor necrosis factor α. Further studies are recommended to evaluate the effect of THBA on adipocyte size and insulin sensitivity in obese cats.

四羟基化胆汁酸对健康瘦猫皮下脂肪细胞大小和胰岛素敏感性的影响
肥胖导致胰岛素抵抗,是猫患糖尿病的主要危险因素。预防肥胖和肥胖引起的胰岛素抵抗是困难的,目前缺乏可靠的长期策略。类视黄醇相关孤儿受体γ (RORγ)最近被确定为小鼠和人类大胰岛素抵抗脂肪细胞发育的重要转录因子。RORγ通过表达靶基因基质金属蛋白酶3 (matrix metalloproteinase 3, MMP3)对脂肪细胞分化产生负向影响,促进胰岛素抵抗型大脂肪细胞的形成。小鼠的初步研究表明,RORγ可被其配体四羟基化胆汁酸(THBA)抑制。在本研究中,测定了健康猫和糖尿病猫的血清THBA水平。此外,我们还研究了补充THBA对健康正常体重猫脂肪细胞大小、rrorγ、MMP3、白细胞介素6、肿瘤坏死因子α、脂联素和瘦素mRNA表达以及胰岛素敏感性的潜在副作用和影响。选取13只健康猫和13只糖尿病猫进行血清THBA水平测定,并选取6只体重正常的健康猫进行饲养试验。在健康猫和糖尿病猫的血清中测定了相似的THBA水平。添加5 mg/kg THBA 8周对试验猫的摄食行为、一般状况和血液参数均无负面影响。显著降低脂肪细胞大小,显著降低脂肪细胞中MMP3、白细胞介素6、肿瘤坏死因子α mRNA表达,显著升高脂联素mRNA表达,RORγ、瘦素mRNA表达不变。给药THBA不影响空腹血糖水平或猫对急性胰岛素的反应。基于这些结果,THBA是可口的,被认为对猫是安全的。通过增加脂联素的表达,降低白细胞介素6和肿瘤坏死因子α的表达,降低MMP3的表达,促进小脂肪细胞的发育。建议进一步研究THBA对肥胖猫脂肪细胞大小和胰岛素敏感性的影响。
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来源期刊
Domestic animal endocrinology
Domestic animal endocrinology 农林科学-奶制品与动物科学
CiteScore
5.50
自引率
4.80%
发文量
58
审稿时长
31 days
期刊介绍: Domestic Animal Endocrinology publishes scientific papers dealing with the study of the endocrine physiology of domestic animal species. Those manuscripts utilizing other species as models for clinical or production problems associated with domestic animals are also welcome. Topics covered include: Classical and reproductive endocrinology- Clinical and applied endocrinology- Regulation of hormone secretion- Hormone action- Molecular biology- Cytokines- Growth factors
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