metabolic dysfunctions
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2022 ◽  
Author(s):  
Ni Fan ◽  
Jia Zhao ◽  
Wei Zhao ◽  
Yanting Shen ◽  
Qingchun Song ◽  
...  

Obesity is hallmarked by endoplasmic reticulum (ER) stress, chronic inflammation and metabolic dysfunctions. The control of obesity is the key to prevent the onset of non-alcoholic fatty liver disease, diabetes,...


Author(s):  
Büşra Başar Gökcen ◽  
Makbule Gezmen Karadağ

Although the reproductive and metabolic dysfunctions associated with polycystic ovary syndrome are clearly known, the mechanisms between these dysfunctions are still unclear. One of the hypotheses put forward for these mechanisms is related to circadian rhythm. To date, many reproductive and metabolic dysfunctions have been associated with circadian rhythm disorders. Especially in women with polycystic ovary syndrome, the relationship between melatonin rhythm, which lasts until late in the morning and starts early at night, and metabolic dysfunctions has been revealed by recent studies. When the relationship between obesity and melatonin is examined, it is clearly seen that melatonin exhibits its effect on energy expenditure rather than energy intake. This hormone affects energy expenditure through adipogenesis, thermogenesis, mitochondrial functions and adipocytokines release, and shows anti-obesity effect. It is thought that this review will shed light on further studies on the therapeutic use of melatonin in obesity associated with polycystic ovary syndrome and contribute to the development of strategies for the prevention of obesity.


Author(s):  
Fernanda Cabrera-Reyes ◽  
Claudia Parra-Ruiz ◽  
María Isabel Yuseff ◽  
Silvana Zanlungo

Lipid-related disorders, which primarily affect metabolic tissues, including adipose tissue and the liver are associated with alterations in lysosome homeostasis. Obesity is one of the more prevalent diseases, which results in energy imbalance within metabolic tissues and lysosome dysfunction. Less frequent diseases include Niemann-Pick type C (NPC) and Gaucher diseases, both of which are known as Lysosomal Storage Diseases (LSDs), where lysosomal dysfunction within metabolic tissues remains to be fully characterized. Adipocytes and hepatocytes share common pathways involved in the lysosome-autophagic axis, which are regulated by the function of cathepsins and CD36, an immuno-metabolic receptor and display alterations in lipid diseases, and thereby impacting metabolic functions. In addition to intrinsic defects observed in metabolic tissues, cells of the immune system, such as B cells can infiltrate adipose and liver tissues, during metabolic imbalance favoring inflammation. Moreover, B cells rely on lysosomes to promote the processing and presentation of extracellular antigens and thus could also present lysosome dysfunction, consequently affecting such functions. On the other hand, growing evidence suggests that cells accumulating lipids display defective inter-organelle membrane contact sites (MCSs) established by lysosomes and other compartments, which contribute to metabolic dysfunctions at the cellular level. Overall, in this review we will discuss recent findings addressing common mechanisms that are involved in lysosome dysregulation in adipocytes and hepatocytes during obesity, NPC, and Gaucher diseases. We will discuss whether these mechanisms may modulate the function of B cells and how inter-organelle contacts, emerging as relevant cellular mechanisms in the control of lipid homeostasis, have an impact on these diseases.


2021 ◽  
Author(s):  
Huishi Toh ◽  
Chentao Yang ◽  
Giulio Formenti ◽  
Kalpana Raja ◽  
Lily Yan ◽  
...  

The Nile rat (Avicanthis niloticus) is an important animal model for biomedical research, including the study of diurnal rhythms and type 2 diabetes. Here, we report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3,613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including those that affect genes associated with type 2 diabetes and metabolic dysfunctions. These include 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. Our findings reflect the exceptional level of genomic detail present in this assembly, which will greatly expand the potential of the Nile rat as a model organism for genetic studies.


2021 ◽  
Author(s):  
Alexia Blandin ◽  
Gregory Hilairet ◽  
Maharajah Ponnaiah ◽  
Simon Ducheix ◽  
Isabelle Dugail ◽  
...  

Adipose extracellular vesicles (AdEV) transport lipids that could participate to the development of obesity-related metabolic dysfunctions. This study aimed to define mice AdEV lipid signature in either healthy or obesity context by a targeted LC-MS/MS approach. Distinct clustering of AdEV and visceral adipose tissue (VAT) lipidomes by principal component analysis reveals specific lipid composition of AdEV compared to source VAT. Comprehensive analysis identifies enrichment of ceramides and phosphatidylglycerols in AdEV compared to VAT in lean conditions. Lipid subspecies commonly enriched in AdEV highlight specific AdEV-lipid sorting. Obesity impacts AdEV lipidome, driving triacylglycerols and sphingomyelins enrichment in obese versus lean conditions. Obese mice AdEV also display elevated phosphatidylglycerols and acid arachidonic subspecies contents highlighting novel biomarkers and/or mediators of metabolic dysfunctions. Our study identifies specific lipid-fingerprints for plasma, VAT and AdEV that are informative of the metabolic status and underline the signaling capacity of lipids transported by AdEV in obesity-associated complications.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan-Ting Chen ◽  
Qi-Yuan Yang ◽  
Yun Hu ◽  
Xiang-Dong Liu ◽  
Jeanene M. de Avila ◽  
...  

AbstractMaternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.


2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Geneviève Marcelin ◽  
Emmanuel L. Gautier ◽  
Karine Clément

Obesity is a chronic and progressive process affecting whole-body energy balance and is associated with comorbidities development. In addition to increased fat mass, obesity induces white adipose tissue (WAT) inflammation and fibrosis, leading to local and systemic metabolic dysfunctions, such as insulin resistance (IR). Accordingly, limiting inflammation or fibrosis deposition may improve IR and glucose homeostasis. Although no targeted therapy yet exists to slow or reverse adipose tissue fibrosis, a number of findings have clarified the underlying cellular and molecular mechanisms. In this review, we highlight adipose tissue remodeling events shown to be associated with fibrosis deposition, with a focus on adipose progenitors involved in obesity-induced healthy as well as unhealthy WAT expansion. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2021 ◽  
Author(s):  
Hendrik J.P. van der Zande ◽  
Eline C. Brombacher ◽  
Joost M. Lambooij ◽  
Leonard R. Pelgrom ◽  
Anna Zawistowska-Deniziak ◽  
...  

Obesity-associated metaflammation drives the development of insulin resistance and type 2 diabetes, notably through modulating innate and adaptive immune cells in metabolic organs. The nutrient sensor liver kinase B1 (LKB1) has recently been shown to control cellular metabolism and T cell priming functions of dendritic cells (DCs). Here, we report that hepatic DCs from high-fat diet (HFD)-fed obese mice display increased LKB1 phosphorylation and that LKB1 deficiency in DCs (CD11cΔLKB1) worsened HFD-driven hepatic steatosis, systemic insulin resistance and glucose intolerance. Loss of LKB1 in DCs was associated with increased cellular expression of Th17-polarizing cytokines and increased hepatic CD4+ IL-17A+ Th17 cells in HFD-fed mice. Importantly, IL-17A neutralization rescued metabolic perturbations in HFD-fed CD11cΔLKB1 mice. Mechanistically, disrupted metabolic homeostasis was independent of the canonical LKB1-AMPK axis. Instead, we provide evidence for involvement of the AMPK-related salt-inducible kinase(s) in controlling Th17-polarizing cytokine expression in LKB1-deficient DCs. Altogether, our data reveal a key role for LKB1 signalling in DCs in protection against obesity-induced metabolic dysfunctions by limiting hepatic Th17 differentiation.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Andrea Gonzalez ◽  
Felipe Simon ◽  
Oscar Achiardi ◽  
Cristian Vilos ◽  
Daniel Cabrera ◽  
...  

Sarcopenic obesity (SO) is a combination of obesity and sarcopenia that primarily develops in older people. Patients with SO have high fat mass, low muscle mass, low muscle strength, and low physical function. SO relates to metabolic syndrome and an increased risk of morbimortality. The prevalence of SO varies because of lacking consensus criteria regarding its definition and the methodological difficulty in diagnosing sarcopenia and obesity. SO includes systemic alterations such as insulin resistance, increased proinflammatory cytokines, age-associated hormonal changes, and decreased physical activity at pathophysiological levels. Interestingly, these alterations are influenced by oxidative stress, which is a critical factor in altering muscle function and the generation of metabolic dysfunctions. Thus, oxidative stress in SO alters muscle mass, the signaling pathways that control it, satellite cell functions, and mitochondrial and endoplasmic reticulum activities. Considering this background, our objectives in this review are to describe SO as a highly prevalent condition and look at the role of oxidative stress in SO pathophysiology.


Author(s):  
L. América Chi Uluac ◽  
M. Cristina Vargas González

Diabetes mellitus and high levels of resistin are risk factors for COVID-19, suggest- ing a shared mechanism for their contribution to the increased severity of COVID-19. Resistin belongs to the family of resistin-like molecules (RELMs) whose implications for inflammatory and metabolic dysfunctions warrant its study in order to shed light on the etiology of these concerning pathologies. In this work, our objective is to char- acterize the structural dynamics of the reported crystallized resistin-like molecules. We performed molecular dynamics simulations of all-atom solvated protein at physiological and high temperatures for the three mouse structures reported so far. We found that in all the structures studied, there is a loss of helicity as a first step of protein denat- uration. There is a high stability of the globular β-sheet domain in resistin protein structures that is not conserved for RELMβ. At high temperature, we found a partial interconversion of α-helices into β-sheets in all proteins, indicating that this propensity is not only found during aggregation but also heating. We had been able to identify a largely persistent hydrogen-bond network shared by all the proteins in the interchain globular domain at room temperature. This network of hydrogen bonds is conserved considerably at high temperature in resistin structures, but not in RELMβ. These findings may guide future studies to increase our understanding of the different and shared mechanisms of action of RELMs.


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