The Potential to Fight Obesity with Adipogenesis Modulating Compounds.

Obesity is an increasingly severe public health problem, which brings huge social and economic burdens. Increased body adiposity in obesity is not only tightly associated with type 2 diabetes, but also significantly increases the risks of other chronic diseases including cardiovascular diseases, fatty liver diseases and cancers. Adipogenesis describes the process of the differentiation and maturation of adipocytes, which accumulate in distributed adipose tissue at various sites in the body. The major functions of white adipocytes are to store energy as fat during periods when energy intake exceeds expenditure and to mobilize this stored fuel when energy expenditure exceeds intake. Brown/beige adipocytes contribute to non-shivering thermogenesis upon cold exposure and adrenergic stimulation, and thereby promote energy consumption. The imbalance of energy intake and expenditure causes obesity. Recent interest in epigenetics and signaling pathways has utilized small molecule tools aimed at modifying obesity-specific gene expression. In this review, we discuss compounds with adipogenesis-related signaling pathways and epigenetic modulating properties that have been identified as potential therapeutic agents which cast some light on the future treatment of obesity.

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.

Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases.

The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.

Hydrogen: A Novel Option in Human Disease Treatment.

H2 has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H2 gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H2 gas are not clear. H2 gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H2 gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.