scholarly journals Parasitic worm-derived ES-62 promotes health- and life-span in high calorie diet-fed mice

2019 ◽  
Author(s):  
Jenny Crowe ◽  
Felicity E. Lumb ◽  
James Doonan ◽  
Margaux Broussard ◽  
Anuradha Tarafdar ◽  
...  
Keyword(s):  
Learning Approaches ◽  
Human Lifespan ◽  
Metabolic Dysregulation ◽  
Global Pandemic ◽  
Parasitic Worm ◽  
Acanthocheilonema Viteae ◽  
Calorie Diet ◽  
Associated Conditions ◽  
High Calorie

AbstractThe recent extension of human lifespan has not been matched by equivalent improvements in late-life health due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, ageing-associated conditions exacerbated by widespread adoption of the high calorie Western diet (HCD). As a novel therapeutic strategy, we have investigated the potential of ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, to improve healthspan by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We found that ES-62 improves a range of inflammatory but also pathophysiological, metabolic and microbiome parameters, when administered subcutaneously at only 1 µg/week throughout the lifespan of HCD-fed mice. Strikingly, ES-62 induced sex-specific healthspan signatures and indeed, it substantially increased the median survival of male, but not female, HCD-mice. Modelling of 113 responses contributing to these differential signatures by machine learning approaches now signposts candidate parameters key to promoting both healthspan and lifespan.

scholarly journals Increased Postprandial GIP and Glucagon Responses, But Unaltered GLP-1 Response after Intervention with Steroid Hormone, Relative Physical Inactivity, And High-Calorie Diet in Healthy Subjects

2011 ◽  
Vol 96 (2) ◽  
pp. 447-453 ◽  
Author(s):  
Katrine B. Hansen ◽  
Tina Vilsbøll ◽  
Jonatan I. Bagger ◽  
Jens J. Holst ◽  
Filip K. Knop
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Physical Inactivity ◽  
Postprandial Glucose ◽  
Calorie Diet ◽  
High Calorie Diet ◽  
High Calorie

abstract Objective: Increased postprandial glucose-dependent insulinotropic polypeptide (GIP) and glucagon responses and reduced postprandial glucagon-like peptide-1 (GLP-1) responses have been observed in some patients with type 2 diabetes mellitus. The causality of these pathophysiological traits is unknown. We aimed to determine the impact of insulin resistance and reduced glucose tolerance on postprandial GIP, GLP-1, and glucagon responses in healthy subjects. Research Design and Methods: A 4-h 2200 KJ-liquid meal test was performed in 10 healthy Caucasian males without family history of diabetes [age, 24 ± 3 yr (mean ± sd); body mass index, 24 ± 2 kg/m2; fasting plasma glucose, 4.9 ± 0.3 mm; hemoglobin A1c, 5.4 ± 0.1%] before and after intervention using high-calorie diet, relative physical inactivity, and administration of prednisolone (37.5 mg/d) for 12 d. Results: The intervention resulted in insulin resistance according to the homeostatic model assessment [1.1 ± 0.3 vs. 2.3 (mean ± sem) ± 1.3; P = 0.02] and increased postprandial glucose excursions [area under curve (AUC), 51 ± 28 vs. 161 ± 32 mm · 4 h; P = 0.045], fasting plasma insulin (36 ± 3 vs. 61 ± 6 pm; P = 0.02), and postprandial insulin responses (AUC, 22 ± 6 vs. 43 ± 13 nm · 4 h; P = 0.03). This disruption of glucose homeostasis had no impact on postprandial GLP-1 responses (AUC, 1.5 ± 0.7 vs. 2.0 ± 0.5 nm · 4 h; P = 0.56), but resulted in exaggerated postprandial GIP (6.2 ± 1.0 vs. 10.0 ± 1.3 nm · 4 h; P = 0.003) and glucagon responses (1.6 ± 1.5 vs. 2.4 ± 3.2; P = 0.007). Conclusions: These data suggest that increased postprandial GIP and glucagon responses may occur as a consequence of insulin resistance and/or reduced glucose tolerance. Our data suggest that acute disruption of glucose homeostasis does not result in reduced postprandial GLP-1 responses as observed in some individuals with type 2 diabetes mellitus.

scholarly journals β-arrestin-1 suppresses myogenic reprogramming of brown fat to maintain euglycemia

2020 ◽  
Vol 6 (23) ◽  
pp. eaba1733 ◽  
Author(s):  
Sai P. Pydi ◽  
Shanu Jain ◽  
Luiz F. Barella ◽  
Lu Zhu ◽  
Wataru Sakamoto ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Peripheral Tissues ◽  
Nuclear Signaling ◽  
Brown Adipose ◽  
Calorie Diet ◽  
Obesogenic Diet ◽  
Obesity Drugs ◽  
High Calorie

A better understanding of the signaling pathways regulating adipocyte function is required for the development of new classes of antidiabetic/obesity drugs. We here report that mice lacking β-arrestin-1 (barr1), a cytoplasmic and nuclear signaling protein, selectively in adipocytes showed greatly impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet. In contrast, transgenic mice overexpressing barr1 in adipocytes were protected against the metabolic deficits caused by a high-calorie diet. Barr1 deficiency led to a myogenic reprogramming of brown adipose tissue (BAT), causing elevated plasma myostatin (Mstn) levels, which in turn led to impaired insulin signaling in multiple peripheral tissues. Additional in vivo studies indicated that barr1-mediated suppression of Mstn expression by BAT is required for maintaining euglycemia. These findings convincingly identify barr1 as a critical regulator of BAT function. Strategies aimed at enhancing barr1 activity in BAT may prove beneficial for the treatment of type 2 diabetes.

Pioglitazone mitigates renal glomerular vascular changes in high-fat, high-calorie-induced type 2 diabetes mellitus

2006 ◽  
Vol 291 (3) ◽  
pp. F694-F701 ◽  
Author(s):  
Walter E. Rodriguez ◽  
Neetu Tyagi ◽  
Irving G. Joshua ◽  
John C. Passmore ◽  
John T. Fleming ◽  
...  
Keyword(s):  
Renal Artery ◽  
Matrix Metalloproteinase 2 ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Calorie Diet ◽  
Contraction And Relaxation ◽  
High Calorie

Our hypothesis is that impairment of peroxisome proliferator-activated receptor-γ (PPARγ) initiates renal dysfunction by increasing renal glomerular matrix metalloproteinase-2 (MMP-2) activity because of increased renal homocysteine (Hcy) and decreased nitric oxide (NO) levels. C57BL/6J mice were made diabetic (D) by being fed a high-fat-calorie diet, and an increase in PPARγ activity was induced by adding pioglitazone (Pi) to the diet. Mice were grouped as follows: normal calorie diet (N), D, N+Pi, and D+Pi ( n = 6/group). The glomerular filtration rate (GFR), renal artery blood flow and pressure, and plasma glucose were measured. Renal glomeruli and preglomerular arterioles were isolated. Plasma and glomerular levels of NO, Hcy, and MMP activity were measured. The contractile response to phenylephrine and the dilatation response to acetylcholine in renal arteriolar rings were measured in a tissue myobath. In N, D, N+Pi, and D+Pi groups, respectively, GFR was 9.4 ± 1.2, 3.9 ± 1.1, 9.2 ± 1.6, and 8.4 ± 1.4 μl·min−1·g body wt−1. Renovascular resistance was 140 ± 3, 367 ± 21, 161 ± 9, and 153 ± 10 mmHg·ml·min−1. Levels of Hcy were increased from 5.8 ± 1.5 in the N to 18.0 ± 4.0 μmol/l in the D group. Glomerular levels of MMP-2 were increased in D mice compared with N mice, and there was no change in levels of MMP-9. Treatment with Pi ameliorated glomerular levels of MMP-2 and Hcy in the D group. Renal artery ring contraction and relaxation by phenylephrine and acetylcholine, respectively, were attenuated in the D groups compared with the N groups. Results suggest that a PPARγ agonist ameliorates preglomerular arteriole remodeling in diabetes by decreasing tissue levels of Hcy and MMP-2 activity and increasing NO.

Abstract P246: Inhibition of Endothelial Senescence Ameliorates Insulin Resistance of Obese Mice

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Masataka Yokoyama ◽  
Tohru Minamino ◽  
Sho Okada ◽  
Kaoru Tateno ◽  
Junji Moriya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Endothelial Cell ◽  
Glucose Uptake ◽  
Cellular Senescence ◽  
P53 Expression ◽  
Calorie Diet ◽  
High Calorie Diet ◽  
High Calorie

Various stimuli can induce irreversible cell growth arrest, termed cellular senescence. This response is controlled by negative regulators of the cell cycle such as p53. Accumulating evidence suggests a potential relationship between cellular senescence and age-associated diseases including type 2 diabetes. Here we show a crucial role for endothelial p53 in the regulation of insulin resistance. We found that treatment of endothelial cells with high glucose and palmitate synergistically increased p53 expression. Consistent with the in vitro results, endothelial expression of p53 was markedly up-regulated when the mice were fed a high-calorie diet, suggesting that excessive calorie intake promotes endothelial senescence. To investigate the role of endothelial p53 in type 2 diabetes, we analyzed metabolic parameters in endothelial cell-specific p53 conditional knockout (ECp53CKO) mice on a high-calorie diet. In spite of no difference in dietary intake, ECp53CKO mice had a significantly smaller weight and less fat accumulation than control mice. Moreover, ECp53CKO mice showed better insulin sensitivity and glucose tolerance than control littermates. ECp53CKO demonstrated a significant increase in oxygen consumption and had a higher core body temperature compared with control mice. Next we considered some assumed mechanisms of relationship of endothelial cell p53 expression and metabolic disorders. As a result, we found that ECp53CKO mice had higher glucose uptake in skeletal muscles than control. These results indicate that inhibition of endothelial senescence ameliorates insulin resistance by increasing energy consumption via glucose uptake and suggest that endothelial p53 will be a novel therapeutic target for type 2 diabetes.

scholarly journals The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing

2020 ◽  
Vol 16 (3) ◽  
pp. e1008391 ◽  
Author(s):  
Jenny Crowe ◽  
Felicity E. Lumb ◽  
James Doonan ◽  
Margaux Broussard ◽  
Anuradha Tarafdar ◽  
...  
Keyword(s):  
Mouse Model ◽  
Life Span ◽  
Parasitic Worm ◽  
Calorie Diet ◽  
High Calorie Diet ◽  
High Calorie

scholarly journals Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Zuqing Su ◽  
Yanru Guo ◽  
Xiufang Huang ◽  
Bing Feng ◽  
Lipeng Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Calorie Diet ◽  
Underlying Mechanisms ◽  
High Calorie

Metabolic disorders include metabolic syndrome, obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular diseases. Due to unhealthy lifestyles such as high-calorie diet, sedentary and physical inactivity, the prevalence of metabolic disorders poses a huge challenge to global human health, which is the leading cause of global human death. Mitochondrion is the major site of adenosine triphosphate synthesis, fatty acid β−oxidation and ROS production. Accumulating evidence suggests that mitochondrial dysfunction-related oxidative stress and inflammation is involved in the development of metabolic disorders. Mitophagy, a catabolic process, selectively degrades damaged or superfluous mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial function. It is considered to be one of the major mechanisms responsible for mitochondrial quality control. Growing evidence shows that mitophagy can prevent and treat metabolic disorders through suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. In the past decade, in order to expand the range of pharmaceutical options, more and more phytochemicals have been proven to have therapeutic effects on metabolic disorders. Many of these phytochemicals have been proved to activate mitophagy to ameliorate metabolic disorders. Given the ongoing epidemic of metabolic disorders, it is of great significance to explore the contribution and underlying mechanisms of mitophagy in metabolic disorders, and to understand the effects and molecular mechanisms of phytochemicals on the treatment of metabolic disorders. Here, we investigate the mechanism of mitochondrial dysfunction in metabolic disorders and discuss the potential of targeting mitophagy with phytochemicals for the treatment of metabolic disorders, with a view to providing a direction for finding phytochemicals that target mitophagy to prevent or treat metabolic disorders.

The evaluation of lipid peroxidation and oxidative modification of proteins in blood serum under obesity development and the consumption of aqueous kidney beans Phaseolus vulgaris pods extract

2020 ◽  
Vol 33 (1) ◽  
pp. 38-44
Author(s):  
Alona Yurchenko ◽  
Daryna Krenytska ◽  
Olexii Savchuk ◽  
Tetiana Halenova ◽  
Natalia Raksha ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Oxidative Modification ◽  
Resistance Development ◽  
Oxidative Modification Of Proteins ◽  
Kidney Beans ◽  
Calorie Diet ◽  
Diet Control ◽  
High Calorie Diet ◽  
High Calorie

AbstractOur interest has focused on the investigation of the anti-obese potential of kidney beans (P. vulgaris) pods extract. In the course of the study, obesity development in rats was induced with high-calorie diet. Control and obese rats then have consumed with aqueous kidney beans (P. vulgaris) pods extract during 6 weeks (200 mg/kg). Results show that the long-term consumption of P. vulgaris pods extract can lead to the reduction of hyperglycemia and insulin resistance development. Furthermore, we saw a normalization of lipid peroxidation parameters and oxidative modification of protein due to the consumption of the kidney beans (P. vulgaris) pods extract. Our experimental data demonstrate the ability of the kidney beans (P. vulgaris) pod extracts to mitigate obesity development but the details of this mechanism remains to be not fully understood.

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