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.

The study of aging and age-related diseases has traditionally focused on short-lived laboratory species such as mice. The common degu (Octodon degus) is a long-lived rodent species native to Chile that naturally develops neuropathology and behavioral deficits characteristic of Alzheimer’s disease together with other comorbidities associated with aging. These characteristics make the degu a useful model to gain insights into the interaction of aging and neurodegeneration.

Many scientific breakthroughs have depended on animal research, yet the ethical concerns surrounding the use of animals in experimentation have long prompted discussions about humane treatment and responsible scientific practice. First articulated by Russell and Burch, the 3Rs Principles of Replacement, Reduction, and Refinement have gained widespread recognition as basic guidelines for animal research. Over time, the 3Rs have transcended the research community, influencing policy decisions, animal welfare advocacy and public perception of animal experimentation. Despite their broad acceptance, interpretations of the 3Rs vary substantially, shaping statutory frameworks at various levels, with both technical and practical impacts.

The adult mammalian heart is known to have very limited regenerative capacity, explaining at least in part the frequency of cardiovascular diseases and their impact as the leading cause of death worldwide. By contrast, the neonatal heart has the ability to regenerate upon injury, and the molecular mechanisms underlying this regenerative capacity are intensely investigated to provide novel cues for the repair of the adult heart. However, the existing rodent neonatal injury models—apex resection, left anterior descending artery ligation and cryoinjury—have limitations, such as being technically demanding, yielding a nonphysiological injury type and/or lack of reproducibility. Here we have therefore established a novel ischemic heart injury method in neonatal mice via cauterization of the root of the left coronary artery. This surgical procedure is technically straightforward, requires less than 10 min for completion and yields reproducible, large ischemic lesions (40% of the left ventricle) with low mortality rates (10% of animals). The injury also induces secondary pulmonary hypertension shortly after surgery, allowing to study the response of the right ventricle. Moreover, neonatal mice at postnatal days 1 and 3 display strongly opposing outcomes after the surgery, because of the lack of cardiac regeneration at the later stage. Thus, this new neonatal heart injury model is of great use for mechanistic studies exploring the regeneration of the left ventricle and the adaptation of the right ventricle upon myocardial infarction.