Metabolic Disorders: Obesity and Diabetes

2011 ◽  
pp. 389-416
Author(s):  
See-Muah Lee ◽  
Chee-Fang Sum
Keyword(s):  
Metabolic Disorders ◽  
Obesity And Diabetes

The outer membrane protein Amuc_1100 of Akkermansia muciniphila promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling

2021 ◽  
Author(s):  
Junchao Wang ◽  
Wenjuan Xu ◽  
Rongjuan Wang ◽  
Rongrong Cheng ◽  
Zhengquan Tang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Metabolic Disorders ◽  
Therapeutic Effects ◽  
Akkermansia Muciniphila ◽  
Intestinal Mucus ◽  
Obesity And Diabetes

Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer...

Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1

2019 ◽  
Vol 11 (488) ◽  
pp. eaau7116 ◽  
Author(s):  
Shiming Peng ◽  
Wen Xiao ◽  
Dapeng Ju ◽  
Baofa Sun ◽  
Nannan Hou ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Metabolic Disorders ◽  
Fasting Blood Glucose ◽  
Reduced Body ◽  
Forkhead Box ◽  
Obesity And Diabetes ◽  
Approved Drugs ◽  
Blood Glucose Concentrations ◽  
Precise Molecular Mechanism

Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Administration–approved drugs to identify entacapone as a potential FTO inhibitor. Using structural and biochemical studies, we showed that entacapone directly bound to FTO and inhibited FTO activity in vitro. Furthermore, entacapone administration reduced body weight and lowered fasting blood glucose concentrations in diet-induced obese mice. We identified the transcription factor forkhead box protein O1 (FOXO1) mRNA as a direct substrate of FTO, and demonstrated that entacapone elicited its effects on gluconeogenesis in the liver and thermogenesis in adipose tissues in mice by acting on an FTO-FOXO1 regulatory axis.

scholarly journals The antagonist of CXCR1 and CXCR2 protects db/db mice from metabolic diseases through modulating inflammation

2019 ◽  
Vol 317 (6) ◽  
pp. E1205-E1217 ◽  
Author(s):  
Siyuan Cui ◽  
Lu Qiao ◽  
Shanshan Yu ◽  
Lili Men ◽  
Yu Li ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Obesity And Diabetes ◽  
Phosphorylated Akt

Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in db/db mice. The db/m and db/db mice were subcutaneously injected with G31P or equivalent normal saline once a day for 6 wk. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated Akt levels. The expressions of several genes encoding proteins involved in de novo lipogenesis were decreased in G31P-treated db/db mice. Meanwhile, immune cell infiltration and cytokine release were attenuated in db/db mice with G31P treatment. G31P also improved the ratio of proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates metabolic disturbances via inhibition of CXCR1 and CXCR2 pathways in db/db mice. These data suggest that the selective inhibition of CXC chemokines may have therapeutic effects on symptoms associated with obesity and diabetes.

scholarly journals ACE2 Pathway Regulates Thermogenesis and Energy Metabolism

2021 ◽  
Author(s):  
Xi Cao ◽  
Tingting Shi ◽  
Chuanhai Zhang ◽  
Wanzhu Jin ◽  
Lini Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Cold Stimulation ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Pka Pathway

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. ACE2 knockout mice (ACE2-/y), Mas knockout mice (Mas-/-), and the mice transplanted with brown adipose tissue from Mas-/- mice displayed impaired thermogenesis. In contrast, impaired thermogenesis of db/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of ACE2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel therapeutic targets for the treatment of metabolic disorders.

scholarly journals Epigenetic Regulators of White Adipocyte Browning

Epigenomes ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 3
Author(s):  
Ravikanth Nanduri
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
White Adipocyte ◽  
Primary Function ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Epigenetic Regulators

Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT can induce metabolic disorders such as dyslipidemia, obesity, and diabetes. Preadipocytes or adipocytes from WAT possess sufficient plasticity as they can transdifferentiate into brown-like beige adipocytes. Studies in both humans and rodents showed that brown and beige adipocytes could improve metabolic health and protect from metabolic disorders. Brown fat requires activation via exposure to cold or β-adrenergic receptor (β-AR) agonists to protect from hypothermia. Considering the fact that the usage of β-AR agonists is still in question with their associated side effects, selective induction of WAT browning is therapeutically important instead of activating of BAT. Hence, a better understanding of the molecular mechanisms governing white adipocyte browning is vital. At the same time, it is also essential to understand the factors that define white adipocyte identity and inhibit white adipocyte browning. This literature review is a comprehensive and focused update on the epigenetic regulators crucial for differentiation and browning of white adipocytes.

scholarly journals Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Sara C Pereira ◽  
Luís Crisóstomo ◽  
Mário Sousa ◽  
Pedro F Oliveira ◽  
Marco G Alves
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Disorders ◽  
Sperm Quality ◽  
Epigenetic Inheritance ◽  
Male Reproduction ◽  
Reproductive Age ◽  
Metabolic Abnormalities ◽  
Obesity And Diabetes ◽  
Harmful Effects

Abstract The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with in vitro and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the ‘fat epidemic’ efficiently.

scholarly journals Effects of vitamin D deficiency on the improvement of metabolic disorders in obese mice after vertical sleeve gastrectomy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Zhang ◽  
Min Feng ◽  
Lisha Pan ◽  
Feng Wang ◽  
Pengfei Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Vitamin D Deficiency ◽  
Hepatic Steatosis ◽  
Metabolic Disorders ◽  
Obese Mice ◽  
Vertical Sleeve Gastrectomy ◽  
Obesity And Diabetes

AbstractVertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries for the remission of obesity and diabetes. Its effects include weight loss, improved insulin resistance, and the improvement of hepatic steatosis. Epidemiologic studies demonstrated that vitamin D deficiency (VDD) is associated with many diseases, including obesity. To explore the role of vitamin D in metabolic disorders for patients with obesity after VSG. We established a murine model of diet-induced obesity + VDD, and we performed VSGs to investigate VDD's effects on the improvement of metabolic disorders present in post-VSG obese mice. We observed that in HFD mice, the concentration of VitD3 is four fold of HFD + VDD one. In the post-VSG obese mice, VDD attenuated the improvements of hepatic steatosis, insulin resistance, intestinal inflammation and permeability, the maintenance of weight loss, the reduction of fat loss, and the restoration of intestinal flora that were weakened. Our results suggest that in post-VSG obese mice, maintaining a normal level of vitamin D plays an important role in maintaining the improvement of metabolic disorders.

scholarly journals The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2

2019 ◽  
Vol 22 (3) ◽  
pp. 253-262
Author(s):  
Elena V. Pokrovskaya ◽  
Minara S. Shamkhalova ◽  
Marina V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Gut Microbiota ◽  
Human Body ◽  
Diabetes Mellitus Type 2 ◽  
Metabolic Disorders ◽  
Developed Countries ◽  
Diabetes Mellitus Type ◽  
Obesity And Diabetes

Obesity is a worldwide problem of the last century, the prevalence of which has reached pandemic proportions in developed countries. Over the past few years, a considerable amount of data has been gathered, reporting a direct link between changes in gut microbiota and the development of obesity, as well as related diseases, primarily, diabetes mellitus type 2. The elaboration of optimal methods of prevention and treatment regimens of these diseases needs to structure the existing knowledge about the mechanisms of development of metabolic disorders, the role of intestinal microbiota in the latter and possible therapeutic targets. This review examines the role of microorganisms in the human body, with the main focus on the developmental origins of metabolic disorders using animal models and accumulated experience of research on their effects on the human body, and also discusses possible treatment options, including bariatric surgery, fecal microbiota transplantation, the use of pre- and probiotics and certain particular groups of glucose-lowering drugs.

scholarly journals Influence of Obesity and Type 2 Diabetes on Calcium Handling by Skeletal Muscle: Spotlight on the Sarcoplasmic Reticulum and Mitochondria

2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroaki Eshima
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Metabolic Disorders ◽  
Fine Tuning ◽  
Calcium Handling ◽  
Obesity And Diabetes ◽  
The Impact

Obesity and diabetes have been shown to interfere with energy metabolism and cause peripheral insulin resistance in skeletal muscle. However, recent studies have focused on the effect metabolic insult has on the loss of muscle size, strength, and physical function. Contractile dysfunction has been linked to impaired intracellular Ca2+ concentration ([Ca2+]i) regulation. In skeletal muscle, [Ca2+]i homeostasis is highly regulated by Ca2+ transport across the sarcolemma/plasma membrane, the golgi apparatus, sarcoplasmic reticulum (SR), and mitochondria. Particularly, the SR and or mitochondria play an important role in the fine-tuning of this metabolic process. Recent studies showed that obesity and insulin resistance are associated with interactions between the SR and mitochondrial networks (the dynamic tubular reticulum formed by mitochondria), suggesting that metabolic disorders alter Ca2+ handling by these organelles. These interactions are facilitated by specific membrane proteins, including ion channels. This review considers the impact of metabolic disorders, such as obesity and type 2 diabetes, on the regulation of [Ca2+]i in skeletal muscle. It also discusses the mechanisms by which this occurs, focusing chiefly on the SR and mitochondria networks. A deeper understanding of the effect of metabolic disorders on calcium handling might be useful for therapeutic strategies.

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