Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases

Abstract

Adipose tissues are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue and brown adipose tissue are currently considered key endocrine organs, they differ functionally and morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between white and brown adipocytes, illustrates the plastic nature of the adipose tissue. These cells are generated through white adipose tissue browning, a process associated with augmented non-shivering thermogenesis and metabolic capacity. This process involves the upregulation of the uncoupling protein 1, a molecule that uncouples the respiratory chain from Adenosine triphosphate synthesis, producing heat. β-3 adrenergic receptor system is one important mediator of white adipose tissue browning, during cold exposure. Surprisingly, hyperthermia may also induce beige activation and white adipose tissue beiging. Physical exercising copes with increased levels of specific molecules, including Beta-Aminoisobutyric acid, irisin, and Fibroblast growth factor 21 (FGF21), which induce adipose tissue browning. FGF21 is a stress-responsive hormone that interacts with beta-klotho. The central roles played by hormones in the browning process highlight the relevance of the individual lifestyle, including circadian rhythm and diet. Circadian rhythm involves the sleep–wake cycle and is regulated by melatonin, a hormone associated with UCP1 level upregulation. In contrast to the pro-inflammatory and adipose tissue disrupting effects of the western diet, specific food items, including capsaicin and n-3 polyunsaturated fatty acids, and dietary interventions such as calorie restriction and intermittent fasting, favor white adipose tissue browning and metabolic efficiency. The intestinal microbiome has also been pictured as a key factor in regulating white tissue browning, as it modulates bile acid levels, important molecules for the thermogenic program activation. During embryogenesis, in which adipose tissue formation is affected by Bone morphogenetic proteins that regulate gene expression, the stimuli herein discussed influence an orchestra of gene expression regulators, including a plethora of transcription factors, and chromatin remodeling enzymes, and non-coding RNAs. Considering the detrimental effects of adipose tissue browning and the disparities between adipose tissue characteristics in mice and humans, further efforts will benefit a better understanding of adipose tissue plasticity biology and its applicability to managing the overwhelming burden of several chronic diseases.

Knocking Down CDKN2A in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process

“…Rosiglitazone, CEBPs, IL4 and Vascular Endothelial Growth Factor (VEGF) are major upstream regulators of up-regulated pathways ( Figure S2 ). Other over-expressed pathways were those involved in cellular oxidative metabolism such as oxidative phosphorylation, fatty acid oxidation, ketogenesis, as well as amino acid and noradrenaline degradation pathways ( Figure 2 C and Figure S3 ) which are essential for adipogenesis and browning adipocyte capacity [ 24 , 25 ].…”

Neonatal Adiposity Is Associated with microRNAs in Adipocyte-Derived Extracellular Vesicles in Maternal and Cord Blood

“…Given that neonates have a substantial proportion of brown adipose tissue (BAT) and that Indians have lower BAT compared to Europeans, we investigated if any of these DE miRNAs have originated in the BAT. Intriguingly, hsa-miR-92a-3p (FC= -0.36) and hsa-miR-181 (FC= 0.71 in adipose group) which are associated with brown fat activity 38,39 are found to be differentially expressed only in cord blood, re ecting active brown fat activity in neonates. Together our results re ect a possible adipocyte dysfunction in mothers of adipose neonates and their role in fetal adipogenesis.…”

MicroRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood are related to neonatal adiposity

“…Given that neonates have a substantial proportion of brown adipose tissue (BAT) and that Indians have lower BAT compared to Europeans, we investigated if any of these DE miRNAs have originated in the BAT. Intriguingly, hsa-miR-92a-3p (FC= -0.36) and hsa-miR-181 (FC= 0.71 in adipose group) which are associated with brown fat activity 38,39 are found to be differentially expressed only in cord blood, reflecting active brown fat activity in neonates. Together our results show a role for DE miRNAs in influencing maternal adipocyte function and fetal adipogenesis.…”