Brown and beige adipose tissues are the primary sites for adaptive non-shivering thermogenesis. Although they have been known principally for their thermogenic effects, in recent years, it has emerged that, just like white adipose tissue (WAT), brown and beige adipose tissues also play an important role in the regulation of metabolic health through secretion of various brown adipokines (batokines) in response to various physiological cues. These secreted batokines target distant organs and tissues such as the liver, heart, skeletal muscles, brain, WAT, and perform various local and systemic functions in an autocrine, paracrine, or endocrine manner. Brown and beige adipose tissues are therefore now receiving increasing levels of attention with respect to their effects on various other organs and tissues. Identification of novel secreted factors by these tissues may help in the discovery of drug candidates for the treatment of various metabolic disorders such as obesity, type-2 diabetes, skeletal deformities, cardiovascular diseases, dyslipidemia. In this review, we comprehensively describe the emerging secretory role of brown/beige adipose tissues and the metabolic effects of various brown/beige adipose tissues secreted factors on other organs and tissues in endocrine/paracrine manners, and as well as on brown/beige adipose tissue itself in an autocrine manner. This will provide insights into understanding the potential secretory role of brown/beige adipose tissues in improving metabolic health.
A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.
Perivascular adipose tissue (PVAT) refers to the local aggregate of adipose tissue surrounding the vascular tree, exhibiting phenotypes from white to brown and beige adipocytes. Although PVAT has long been regarded as simply a structural unit providing mechanical support to vasculature, it is now gaining reputation as an integral endocrine/paracrine component, in addition to the well-established modulator endothelium, in regulating vascular tone. Since the discovery of anti-contractile effect of PVAT in 1991, the use of multiple rodent models of reduced amounts of PVAT has revealed its regulatory role in vascular remodeling and cardiovascular implications, including atherosclerosis. PVAT does not only release PVAT-derived relaxing factors (PVRFs) to activate multiple subsets of endothelial and vascular smooth muscle potassium channels and anti-inflammatory signals in the vasculature, but it does also provide an interface for neuron-adipocyte interactions in the vascular wall to regulate arterial vascular tone. In this review, we outline our current understanding towards PVAT and attempt to provide hints about future studies that can sharpen the therapeutic potential of PVAT against cardiovascular diseases and their complications.
Kappaphycus is a commercially important edible red alga widely cultivated for carrageenan production. Here, we aimed to investigate the anti-obesity mechanism of Kappaphycusalvarezii by comparing the effects of whole seaweed (T), extracted native κ-carrageenan (CGN), and the leftover fraction sans-carrageenan (SCGN) supplementations (5%, w/w) on diet-induced obese C57BL/6J mice. A high-fat diet induced both a raised body fat percentage and serum cholesterol level, increased adipocytes size, abnormal levels of adipocytokines, and promoted gut dysbiosis. Our results showed that, overall, both CGN and SCGN were more effective in reversing obesity and related metabolic syndromes to normal levels than T. Furthermore, these findings suggested that CGN- and SCGN-modulated gut dysbiosis induced by a high-fat diet, which may play an influencing role in adiponectin dysregulation. Our data also showed some evidence that CGN and SCGN have distinct effects on selected genes involved in lipid metabolism. In conclusion, both κ-carrageenan and SCGN have novel anti-obesity potential with possible different mechanisms of action.
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.
The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.