Metabolic syndrome and extensive adipose tissue inflammation in morbidly obese Göttingen minipigs.

OBJECTIVE: The worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM). METHODS: Young adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established. RESULTS: DIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM. CONCLUSIONS: The Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity.

Comparison of traditional and sensor-based electronic stethoscopes in beagle dogs.

The objective of this study was to compare the auscultatory findings using traditional and electronic sensor-based stethoscopes. Thirty-three adult healthy Beagles (20 females, 13 males, mean age: 4.8 years, range 1.4-8 years) were auscultated by four investigators with different experiences (INVEST-1, -2, -3 and -4) independently with both stethoscopes. Final cardiological diagnoses were established by echocardiography. Mitral murmurs were heard with both stethoscopes by all investigators and echocardiography revealed mild mitral valve insufficiency in 7 dogs (21%, 4 females, 3 males). The statistical sensitivity (Se) in recognising cardiac murmurs proved to be 82% using the traditional stethoscope and 75% using the electronic one in the mean of the four examiners, whilst statistical specificity (Sp) was 99% by the traditional and 100% by the electronic stethoscope. The means of the auscultatory sensitivity differences between the two stethoscopes were 0.36 on the left and 0.59 on the right hemithorax, demonstrating an advantage for the electronic stethoscope being more obvious above the right hemithorax (P = 0.0340). The electronic stethoscope proved to be superior to the traditional one in excluding cardiac murmurs and especially in auscultation over the right hemithorax. Mitral valve disease was relatively common in this clinically healthy research Beagle population.