A dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component (energy intake or energy expenditure) lead to biological and/or behavioral compensatory changes in the counterpart. The interplay between energy demand and caloric intake appears designed to guarantee an adequate fuel supply in variable life contexts. In the past decades, researchers focused their attention on finding efficient strategies to fight the obesity pandemic. The ketogenic or “keto” diet (KD) gained substantial consideration as a potential weight-loss strategy, whereby the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and the activity of ketogenic enzymes. It has been hypothesized that during the first phase of KDs when glucose utilization is still prevalent, an increase in EE may occur, due to increased hepatic oxygen consumption for gluconeogenesis and for triglyceride-fatty acid recycling. Later, a decrease in 24-h EE may ensue due to the slowing of gluconeogenesis and increase in fatty acid oxidation, with a reduction of the respiratory quotient and possibly the direct action of additional hormonal signals.

Objective: Obesity is a recognized risk factor for the progression to severe forms of COVID-19, yet the mechanisms of the association are unclear. Methods: Subcutaneous abdominal adipose tissue specimens of subjects deceased from COVID-19 (n = 23) were compared to those of controls dying abruptly from causes other than infectious (accidental trauma, sudden cardiac death). Alterations of lung parenchyma consistent with moderate to severe disease were detected in all COVID-19 cases, not in controls. Investigations included: histopathologic features, detection of virus antigens and genome, characterization of infiltrating leukocytes, transcription levels of immune-related genes. Results: By RT-PCR, the SARS-CoV-2 genome was detected in the adipose tissue of 13/23 (56%) cases of the COVID-19 cohort. The virus nucleocapsid antigen was detected in the cytoplasm of 1–5% adipocytes in 12/12 COVID-19 cases that were virus-positive by PCR in the adipose tissue (one case could not be assessed due insufficient tissue). The adipose tissue of COVID-19 cases showed leukocyte infiltrates and upregulation of the interferon-alpha pathway. After adjusting for age and sex, the activation score of IFN-alpha was directly related with transcription levels of the ACE2 gene, a key entry factor of SARS-CoV-2. Conclusions: In lethal COVID-19 cases, the SARS-CoV-2 nucleocapsid antigen has been detected in a sizeable proportion of adipocytes, showing that the virus may directly infect the parenchymal cells of subcutaneous fat. Infection appears to activate the IFN alpha pathway and to attract infiltrating leukocytes. Due to the huge numbers of adipocytes in adults, the adipose tissue represents a significant reservoir for SARS-CoV-2 and an important source of inflammatory mediators.

Thyroid cancer is the most common type of endocrine-related malignancy, whose incidence rates have increased dramatically in the last few decades. Neoplasms of follicular origin generally have excellent prognosis, with the exception of less differentiated tumors. Follicular-derived thyroid cancer can manifest as a variety of morphologically distinct entities, characterized by various degrees of differentiation and invasiveness. Histological evaluation is thus crucial for the definition of patients’ prognosis. However, within each histological subtype, tumor behavior can be highly variable, and, in this respect, molecular characterization can provide insightful information to refine the risk stratification of tumors. In addition to the importance of its prognostic role, molecular testing can be used to support the differential diagnosis of thyroid nodules in the absence of marked cyto-morphological aberrations. Finally, with the advent of targeted drugs, the presence of molecular alterations will guide the therapeutic strategies for patients with advanced tumors who do not respond to standard treatment. This review aims to describe the genetic landscape of follicular-derived thyroid tumors also highlighting differences across histological subtypes.

Context Glomerular hyperfiltration may represent a direct pathogenetic link between obesity and kidney disease. The most widely used methods to estimate creatine clearance such as Cockroft–Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) have not been validated in subjects with obesity. Objective The performance of prediction formulas was compared with measured creatinine clearance (mCrCl) in subjects with obesity. Methods The study population included 342 patients with obesity (mean BMI 47.6 kg/m²) without primary kidney disease. A urine collection was performed over 24 hours for measurement of CrCl. Results mCrCl increased with body weight. The CG formula showed an overestimation at high CrCl, whereas an underestimation resulted from CKD-EPI and MDRD. To improve the accuracy of estimated CrCl (eCrCl), a new CG-based formula was developed: $53+0.7×(140−Age)×Weight/(96xSCr)×(0.85iffemale)$A cut-off point for BMI of 32 kg/m² was identified, at which the new formula may be applied to improve eCrCl. Conclusion In patients with obesity the glomerular filtration rate increases with body weight, and it is associated with the presence of albuminuria, suggesting an early kidney injury. We propose a novel formula that improves the accuracy of eCrCl to avoid missed diagnoses of hyperfiltration in patients with obesity.

Conservation of the energy equilibrium can be considered a dynamic process and variations of one component (energy intake or energy expenditure) cause biological and/or behavioral compensatory changes in the other part of the system. The interplay between energy demand and caloric intake appears designed to guarantee an adequate food supply in variable life contexts. The circadian rhythm plays a major role in systemic homeostasis by acting as “timekeeper” of the human body, under the control of central and peripheral clocks that regulate many physiological functions such as sleep, hunger and body temperature. Clock-associated biological processes anticipate the daily demands imposed by the environment, being synchronized under ideal physiologic conditions. Factors that interfere with the expected demand, including daily distribution of macronutrients, physical activity and light exposure, may disrupt the physiologic harmony between predicted and actual behavior. Such a desynchronization may favor the development of a wide range of disease-related processes, including obesity and its comorbidities. Evidence has been provided that the main components of 24-h EE may be affected by disruption of the circadian rhythm. The sleep pattern, meal timing and meal composition could mediate these effects. An increased understanding of the crosstalk between disruption of the circadian rhythm and energy balance may shed light on the pathophysiologic mechanisms underlying weight gain, which may eventually lead to design effective strategies to fight the obesity pandemic.