The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.

Background: Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Results: Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011–2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4–12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently. Conclusions: Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

The aim of the study was to compare the effects of high-intensity interval training (HIIT) and nutrition advice on cardiometabolic biomarkers, hormonal parameters, and cardiorespiratory fitness in adolescent girls with obesity. Adolescent girls with obesity (n = 44, aged 13–19 years) were randomized into a 12-week intervention as follows: (i) dietary advice and HIIT (n = 22), and (ii) dietary advice only (n = 22). The concentration of biomarkers of inflammation, biochemical and hormonal testing, oral glucose tolerance test, cardiorespiratory fitness, physical activity levels, and nutrition were assessed. After a 3-month intervention, the diet+HIIT group significantly increased insulin sensitivity index (–0.34 ± 1.52 vs. 1.05 ± 3.21; p = 0.001) and work load (0.6 ± 11.3 W vs. 14.6 ± 20.2 W; p = 0.024) and decreased glucose area under the curve (–0.29 ± 4.69 vs. −0.98 ± 4.06; p = 0.040), insulin area under the curve (−9.65 ± 117.9 vs. −98.7 ± 201.8; p = 0.003), and high-sensitivity C-reactive protein (hs-CRP) (0.12 ± 1.92 mg/L vs. −1.47 ± 3.67 mg/L; p = 0.039) in comparison with the diet group. Regarding within-group changes, both groups had significant improvements in body mass index (BMI), BMI-standard deviation score, body fat percentage, and systolic blood pressure. Positive impact on waist circumference, waist circumference/height ratio, diastolic blood pressure, hs-CRP, work load, maximal heart rate, and resting heart rate was observed only after the diet+HIIT intervention. No significant change was noted in peak oxygen uptake, lipid profile, and hormonal parameters between groups after intervention. Novelty HIIT and nutrition advice increased insulin sensitivity and decreased BMI, body fat, systolic blood pressure, and diastolic blood pressure. Nutrition advice decreased BMI, body fat, and systolic blood pressure in adolescent girls with obesity.