Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.

Circadian rhythms underpin most physiological processes, including energy metabolism. The core circadian clock consists of a transcription-translation negative feedback loop, and is synchronized to light-dark cycles by virtue of light input from the retina, to the central clock in the suprachiasmatic nucleus in the hypothalamus. All cells in the body have circadian oscillators which are entrained to the central clock by neural and humoral signals. In addition to light entrainment of the central clock in the brain, it now emerges that other stimuli can drive circadian clock function in peripheral tissues, the major one being food. This can then drive the liver clock to be misaligned with the central brain clock, a situation of internal misalignment with metabolic disease consequences. Such misalignment is prevalent, with shift workers making up 20% of the working population. The effects of diet composition on the clock are not completely clarified yet. High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models. Ketogenic diet (KD) is able to induce a metabolic switch from carbohydrate to fatty acid oxidation, miming a fasting state. In recent years, some animal studies have been conducted to investigate the ability of the KD to modify circadian gene expression, and demonstrated that the KD alters circadian rhythm and induces a rearrangement of metabolic gene expression. These findings may lead to new approaches to obesity and metabolic pathologies treatment.

Sleep is a vital process essential for survival. The trend of reduction in the time dedicated to sleep has increased in industrialized countries, together with the dramatic increase in the prevalence of obesity and diabetes. Short sleep may increase the risk of obesity, diabetes and cardiovascular disease, and on the other hand, obesity is associated with sleep disorders, such as obstructive apnea disease, insomnia and excessive daytime sleepiness. Sleep and metabolic disorders are linked; therefore, identifying the physiological and molecular pathways involved in sleep regulation and metabolic homeostasis can play a major role in ameliorating the metabolic health of the individual. Approaches aimed at reducing body weight could provide benefits for both cardiometabolic risk and sleep quality, which indirectly, in turn, may determine an amelioration of the cardiometabolic phenotype of individuals. We revised the literature on weight loss and sleep, focusing on the mechanisms and the molecules that may subtend this relationship in humans as in animal models.

Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.