Diet Impact on Obesity beyond Calories and Trefoil Factor Family 2 (TFF2) as an Illustration: Metabolic Implications and Potential Applications.

Obesity is a health problem with increasing impacts on public health, economy and even social life. In order to reestablish the energy balance, obesity management focuses mainly on two pillars; exercise and diet. Beyond the contribution to the caloric intake, the diet nutrients and composition govern a variety of properties. This includes the energy balance-independent properties and the indirect metabolic effects. Whereas the energy balance-independent properties are close to "pharmacological" effects and include effects such as antioxidant and anti-inflammatory, the indirect metabolic effects represent the contribution a diet can have on energy metabolism beyond the caloric contribution itself, which include the food intake control and metabolic changes. As an illustration, we also described the metabolic implication and hypothetical pathways of the high-fat diet-induced gene Trefoil Factor Family 2. The properties the diet has can have a variety of applications mainly in pharmacology and nutrition and further explore the "pharmacologically" active food towards potential therapeutic applications.

The Comparison of the Effects between Continuous and Intermittent Energy Restriction in Short-Term Bodyweight Loss for Sedentary Population: A Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To compare the effects of continuous energy restriction (CER) and intermittent energy restriction (IER) in bodyweight loss plan in sedentary individuals with normal bodyweight and explore the influence factors of effect and individual retention. METHODS: 26 participants were recruited in this randomized controlled and double-blinded trial and allocated to CER and IER groups. Bodyweight (BW), body mass index (BMI), and resting metabolic rate (RMR) would be collected before and after a 4-week (28 days) plan which included energy restriction (CER or IER) and moderate-intensity exercise. Daily intake of three major nutrients (protein, carbohydrate, fat) and calories were recorded. RESULTS: A significant decrease in BW and BMI were reported within each group. No statistically significant difference in the change of RMR in CERG. No statistically significant difference was reported in the effect between groups, neither as well the intake of total calories, three major nutrients, and individual plan retention. The influence factors of IER and CER are different. CONCLUSION: Both CER and IER are effective and safe energy restriction strategies in the short term. Daily energy intake and physical exercise are important to both IER and CER.

Dietary Regulation of Immunity.

Integrated immunometabolic responses link dietary intake, energy utilization, and storage to immune regulation of tissue function and is therefore essential for the maintenance and restoration of homeostasis. Adipose-resident leukocytes have non-traditional immunological functions that regulate organismal metabolism by controlling insulin action, lipolysis, and mitochondrial respiration to control the usage of substrates for production of heat versus ATP. Energetically expensive vital functions such as immunological responses might have thus evolved to respond accordingly to dietary surplus and deficit of macronutrient intake. Here, we review the interaction of dietary intake of macronutrients and their metabolism with the immune system. We discuss immunometabolic checkpoints that promote healthspan and highlight how dietary fate and regulation of glucose, fat, and protein metabolism might affect immunity.

The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury.

BACKGROUND: Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance. METHODS: To identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury. RESULTS: The gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI. CONCLUSIONS: This comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

BACKGROUND & AIMS: Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. METHODS: 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISIClamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2AT) was measured in subcutaneous adipose tissue before and after weight loss. RESULTS: ACE-2AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10-7). A smaller reduction of ACE-2 AT (ΔACE-2AT) was associated with a larger improvement of ISIClamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2AT (p = 0.011). CONCLUSIONS: Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.

Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: Crosstalk among calorie restriction, autophagy and immune response.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public health across the world. Although there is no clear gender or socioeconomic discrimination in the incidence of COVID-19, individuals who are older adults and/or with comorbidities and compromised immunity have a relatively higher risk of contracting this disease. Since no specific drug has yet been discovered, strengthening immunity along with maintaining a healthy living is the best way to survive this disease. As a healthy practice, calorie restriction in the form of intermittent fasting (IF) in several clinical settings has been reported to promote several health benefits, including priming of the immune response. This dietary restriction also activates autophagy, a cell surveillance system that boosts up immunity. With these prevailing significance in priming host defense, IF could be a potential strategy amid this outbreak to fighting off SARS-CoV-2 infection. Currently, no review so far available proposing IF as an encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on host immune response have also been briefly outlined. This review aimed at revisiting the immunomodulatory potential of IF that may constitute a promising preventive approach against COVID-19.