Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Recent studies have investigated the control of adipose tissue expansion and inflammatory process by microRNAs (miRNAs). These two processes are of great interest because both are associated with obesity and metabolic syndrome. However, despite the great relevance of the role of miRNAs in obesity and adipose tissue, no qualitative and quantitative analysis on the subject has been performed. Thus, we aimed to examine global research activity and current trends with respect to the interaction between obesity, adipose tissue and miRNAs through a bibliometric analysis. This research was performed on the Scopus database for publications containing miRNA, obesity, and adipose tissue keyword combinations. In total, 898 articles were analyzed and the most frequently occurring keywords were selected and clustered into three well-defined groups. As a result, first group of keywords pointed to the research area on miRNAs expressed in obesity-associated diseases. The second group demonstrated the regulation of the adipogenesis process by miRNAs, while the third group highlighted brown adipose tissue and thermogenesis as one of the latest global research trends related to the theme. The studies selected in this paper describe the expression and performance of different miRNAs in obesity and comorbidities. Most studies have focused on identifying miRNAs and signaling pathways associated with obesity, type 2 diabetes mellitus, and cardiovascular disease. Thus, the miRNA profile for these diseases may be used as biomarkers and therapeutic targets in the prevention and treatment of obesity-associated diseases.

Obesity is an epidemic disease and the expansion of adipose tissue, especially visceral fat, promotes the secretion of factors that lead to comorbidities such as diabetes and cardiovascular diseases. Thus, diet and exercise have been proposed as an intervention to reverse these complications. An adipocytokine, known as irisin, mediates the beneficial effects of exercise. It has been proposed as a therapeutic potential in controlling obesity. In view of the above, this paper attempts to determine the modulation of irisin, visceral adiposity and biochemical markers in response to dietary intervention and aerobic exercise. To do this, 52 diet-induced obese male Wistar rats were divided into the following four groups: high-fat diet and exercise (HFD-Ex); HFD-Sedentary (HFD-Sed); chow-diet and exercise (CD-Exercise); and CD-Sed. The exercise-trained group performed a treadmill protocol for 60 min/day, 3 days/week for 8 weeks. Body mass (BM), body fat (BF), fat mass (FM), and fat-free mass (FFM) were analyzed. Mesenteric (MES), epididymal (EPI), and retroperitoneal (RET) adipose tissue was collected and histological analysis was performed. Biochemical irisin, triglycerides, glucose, insulin and inflammatory markers were determined and, FNDC5 protein expression was analyzed. In this study, the diet was the most important factor in reducing visceral adiposity in the short and long term. Exercise was an important factor in preserving muscle mass and reducing visceral depots after a long term. Moreover, the combination of diet and exercise can enhance these effects. Diet and exercise exclusively were the factors capable of increasing the values of irisin/FNDC5, however it did not bring cumulative effects of both interventions. Prescriptions to enhance the obesity treatments should involve reducing visceral adiposity by reducing the fat content in the diet associated with aerobic exercise.

Obesity accumulates fat in the body may cause hypertension and change intracranial pressure waveform morphology (ICP). However, not clear how and when it occurs. Thus, our objective was to evaluate the ICP waveform morphology and P2/P1 ratio during the development of obesity. Sixteen 45-day-old male Wistar rats, after 60 days of adaptation were divided into non-obese (NOB, n = 7) and obese (OB, n = 9). The OB group received a high-fat diet and the NOB group received a standard diet for 24 weeks. ICP, body composition, blood pressure (BP), and heart rate(HR) were assessed every 4 weeks. Two-Way ANOVA was used for the area under the curve with Bonferroni's test, or Student's t-test for BP, and HR. Body mass(BM) and body fat(BF) and fat-free mass(FFM) were higher in OB rats. There was no difference in BP, but there was a difference in HR, greater in OB. The ICP decreased by NOB. These results suggest that the increase in BM and BF caused obesity, and BM can explain the increase in FFM. Although we did not find pathological states of ICP, NOB demonstrated better brain compliance, and the upward trend in the P2 waveform in OB may indicate impairment to the ICP of OB rats.

This study aimed to determine the concentrations of inflammatory markers in visceral adipose tissue (VAT) and skeletal muscle, and changes in body mass and adipocyte size in diet-induced obese rats after moderate-intensity continuous training (MICT) and/or dietary intervention. After 8 weeks of obesity induction through a high-fat diet (HFD) consumption, twenty diet-induced obese male Wistar rats were divided into four groups as follows: (i) control rats fed with HFD (HFD-SED), (ii) obese rats fed with HFD and submitted to MICT (HFD-MICT), (iii) obese rats that were submitted to a nutritional intervention by switching HFD to chow diet (CD-SED), and (iv) obese rats that were submitted to MICT and nutritional intervention (CD-MICT). All the animals in the training groups were submitted to MICT, with an intensity of 50–85% of Vmax, 60 min/day, 3 days/week for 8 weeks. Gastrocnemius muscle (GAST) and mesenteric adipose tissue (mWAT) were collected to quantify tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 using ELISA. The body mass was recorded before and after the experimental protocols, and the adipocyte morphology was assessed using histological analysis. The results showed that HFD-SED had higher body mass, higher concentrations of inflammatory markers in mWAT, and higher increase in adipocyte size. The CD-SED and CD-MICT groups presented with reduced body mass, relative weight of mWAT, and adipocyte size. Moreover, the inflammatory markers in mWAT were reduced after dietary intervention (TNF-α), MICT (IL-10 and TNF-α), or both interventions combined (IL-6 and TNF-α). In contrast, there was no reduction in GAST-relative weight or concentrations of inflammatory markers for any treatment. Finally, we concluded that 8 weeks of dietary intervention alone and combined with MICT were effective in reducing some of the deleterious effects caused by obesity.