Starbæk Sofie M R, Henriksen Betina L, Brogaard Louise, Jessen Eline E, Jensen Tim K, Goletz Steffen, Heegaard Peter M H, Skovgaard Kerstin
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.
Lab Anim (NY). 2025 Aug 6. doi: 10.1038/s41684-025-01588-3.
Meta-inflammation (chronic, low-grade systemic inflammation) is increasingly recognized as an essential link between obesity and the development of various noncommunicable diseases. However, large animal models for studying obesity-related meta-inflammation are lacking. Minipigs have great potential as models for human diseases, warranting investigation of the performance of the Göttingen minipig as a model for obesity-associated meta-inflammation. Here, we fed 26 pigs a high-fat, fructose and cholesterol diet (HFFC) or a standard diet (SD) for 103 days, resulting in the HFFC group having a 45% higher body weight and 16% larger abdominal circumference by the end of the experiment. Meta-inflammation was shown in the HFFC group by elevated serum concentrations of the acute phase protein C-reactive protein for more than 60 days during development of obesity, accompanied by increased numbers of circulating neutrophils and monocytes. Additional obesity-related abnormalities included dyslipidemia, hepatosteatosis and transcriptional changes to genes related to inflammation and metabolism in circulating leukocytes, liver and visceral adipose tissue. Notably, the transcription of genes related to lipid metabolism, namely ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1), was elevated in liver, visceral adipose tissue and circulating leukocytes (ABCA1 only) in the HFFC group compared with the SD group. The development of obesity was accompanied by endotoxemia, indicated by a 2.5-fold increase in serum lipopolysaccharide concentration in the HFFC group compared with the SD group, suggesting increased intestinal permeability. In conclusion, the described Göttingen minipig model convincingly links diet-induced obesity, meta-inflammation and endotoxemia, achieved by short-duration HFFC dieting.
代谢性炎症（慢性、低度全身性炎症）日益被认为是肥胖与各种非传染性疾病发生之间的关键环节。然而，用于研究肥胖相关代谢性炎症的大型动物模型尚缺。小型猪作为人类疾病模型具有巨大潜力，因此有必要研究哥廷根小型猪作为肥胖相关代谢性炎症模型的表现。在此，我们对26头猪喂食高脂、果糖和胆固醇饮食（HFFC）或标准饮食（SD），为期103天，结果在实验结束时，HFFC组猪的体重高出45%，腹围大出16%。在肥胖发展过程中，HFFC组猪在超过60天的时间里血清急性期蛋白C反应蛋白浓度升高，显示出代谢性炎症，同时循环中性粒细胞和单核细胞数量增加。其他与肥胖相关的异常包括血脂异常、肝脂肪变性以及循环白细胞、肝脏和内脏脂肪组织中与炎症和代谢相关基因的转录变化。值得注意的是，与SD组相比，HFFC组猪的肝脏、内脏脂肪组织和循环白细胞（仅ABCA1）中与脂质代谢相关的基因，即ATP结合盒亚家族A成员1（ABCA1）和ATP结合盒亚家族G成员1（ABCG1）的转录水平升高。肥胖的发展伴随着内毒素血症，HFFC组猪血清脂多糖浓度相比SD组增加了2.5倍，表明肠道通透性增加。总之，所述哥廷根小型猪模型令人信服地将饮食诱导的肥胖、代谢性炎症和内毒素血症联系起来，这是通过短期HFFC饮食实现的。
