scholarly journals Role of Flavonoids in the Interactions among Obesity, Inflammation, and Autophagy

2020 ◽  
Vol 13 (11) ◽  
pp. 342
Author(s):  
María García-Barrado ◽  
María Iglesias-Osma ◽  
Elena Pérez-García ◽  
Sixto Carrero ◽  
Enrique Blanco ◽  
...  

Nowadays, obesity is considered as one of the main concerns for public health worldwide, since it encompasses up to 39% of overweight and 13% obese (WHO) adults. It develops because of the imbalance in the energy intake/expenditure ratio, which leads to excess nutrients and results in dysfunction of adipose tissue. The hypertrophy of adipocytes and the nutrients excess trigger the induction of inflammatory signaling through various pathways, among others, an increase in the expression of pro-inflammatory adipocytokines, and stress of the endoplasmic reticulum (ER). A better understanding of obesity and preventing its complications are beneficial for obese patients on two facets: treating obesity, and treating and preventing the pathologies associated with it. Hitherto, therapeutic itineraries in most cases are based on lifestyle modifications, bariatric surgery, and pharmacotherapy despite none of them have achieved optimal results. Therefore, diet can play an important role in the prevention of adiposity, as well as the associated disorders. Recent results have shown that flavonoids intake have an essential role in protecting against oxidative damage phenomena, and presents biochemical and pharmacological functions beneficial to human health. This review summarizes the current knowledge of the anti-inflammatory actions and autophagic flux of natural flavonoids, and their molecular mechanisms for preventing and/or treating obesity.

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bin Wang ◽  
Lei Zhang ◽  
Tong Dai ◽  
Ziran Qin ◽  
Huasong Lu ◽  
...  

AbstractEmerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy—but is fast-growing—it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xueer Wang ◽  
Honghai Zhang ◽  
Zhugui Shao ◽  
Wanxin Zhuang ◽  
Chao Sui ◽  
...  

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.


Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1310
Author(s):  
Maria Rosaria Carillo ◽  
Carla Bertapelle ◽  
Filippo Scialò ◽  
Mario Siervo ◽  
Gianrico Spagnuolo ◽  
...  

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of β-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration.


Hepatology ◽  
2019 ◽  
Vol 71 (2) ◽  
pp. 510-521 ◽  
Author(s):  
Alina M. Allen ◽  
Vijay H. Shah ◽  
Terry M. Therneau ◽  
Sudhakar K. Venkatesh ◽  
Taofic Mounajjed ◽  
...  

2021 ◽  
pp. 17-42
Author(s):  
Paolo Boffetta ◽  
Zuo-Feng Zhang ◽  
Carlo La Vecchia

Neoplasms continue to dominate globally as one of the major sources of human disease and death. There are multiple modifiable causes of cancer and understanding their attributable risk factors for each cancer is of importance. This chapter covers the role of cellular and molecular mechanisms as well as the experimental and epidemiological approaches as determinants of the main cancers. Even if major discoveries in the clinical management of cancer patients will be accomplished in the near future, the changes will mainly affect the affluent part of the world population. Promising approaches focused on prevention of the known causes, reducing its consequences, notably in resource-constrained settings are highlighted.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1887 ◽  
Author(s):  
Francesco Bonollo ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Sofia Karkampouna

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.


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