scholarly journals High Cysteine Diet Reduces Insulin Resistance in SHR-CRP Rats

2021 ◽  
pp. 687-700
Author(s):  
J KRIJT ◽  
J SOKOLOVÁ ◽  
J ŠILHAVÝ ◽  
P MLEJNEK ◽  
J KUBOVČIAK ◽  
...  

Increased plasma total cysteine (tCys) has been associated with obesity and metabolic syndrome in human and some animal studies but the underlying mechanisms remain unclear. In this study, we aimed at evaluating the effects of high cysteine diet administered to SHR-CRP transgenic rats, a model of metabolic syndrome and inflammation. SHR-CRP rats were fed either standard (3.2 g cystine/kg diet) or high cysteine diet (HCD, enriched with additional 4 g L-cysteine/kg diet). After 4 weeks, urine, plasma and tissue samples were collected and parameters of metabolic syndrome, sulfur metabolites and hepatic gene expression were evaluated. Rats on HCD exhibited similar body weights and weights of fat depots, reduced levels of serum insulin, and reduced oxidative stress in the liver. The HCD did not change concentrations of tCys in tissues and body fluids while taurine in tissues and body fluids, and urinary sulfate were significantly increased. In contrast, betaine levels were significantly reduced possibly compensating for taurine elevation. In summary, increased Cys intake did not induce obesity while it ameliorated insulin resistance in the SHR-CRP rats, possibly due to beneficial effects of accumulating taurine.

2021 ◽  
Vol 162 (33) ◽  
pp. 1318-1327
Author(s):  
Tamás Halmos ◽  
Ilona Suba

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Giampaolo De Filippo ◽  
Domenico Rendina ◽  
Domenico Viggiano ◽  
Antonio Fasolino ◽  
Paola Sabatini ◽  
...  

Background: Obesity is the main risk factor for essential hypertension (EH) in childhood. The O.Si.Me. study (Obesity and Metabolic Syndrome in children and adolescents) evaluated the prevalence of metabolic syndrome (MetS) and its constitutive traits in a sample of obese children and adolescents living in Campania, southern Italy. Patients and methods: Four hundred and fifteen children and adolescents consecutively referred to the National Health Service participating Outpatient Clinics for minor health problems and found to have a Body Mass Index (BMI) Z-score > 2.0 were enrolled in the study. The entire sample was screened for MetS, which was defined as the presence of at least 2 of the following alterations in addition to obesity: fasting hyperglycemia, low levels of high-density lipoproteins cholesterol, hypertriglyceridemia, and EH. The present analysis evaluated the clinical characteristics of the O.Si.Me subgroup of EH participants (systolic and/or diastolic BP ≥ 95 th percentile for age, gender and height) as compared with normotensive participants. Results: The prevalence of EH in the O.Si.Me population was 23.6 % (98/415, 48M and 50F.) and two-thirds of the EH participants met the MetS diagnostic criteria. The EH participants featured serum insulin and HOMA-IR levels significantly higher compared with normotensive ones (11.6±0.6 vs. 9.5±0.4 μIU/ml, p = 0.014; 2.6±0.1 vs. 2.2±0.1, p = 0.028 for insulin and HOMA-IR, respectively). These differences were common to boys and girls and remained significant after correction for age, pubertal stage, body weight, length, BMI, gestational age at birth, duration of breastfeeding and anthropometric parental parameters. Accordingly, children and adolescents with EH had a a relative risk of being insulin resistant (defined as a HOMA-IR ≥2.5) significantly greater compared to those without. Moreover, they exhibited higher serum creatinine levels (53.8±7.1 vs. 35.4±6.8 μmol/l, p=0.025) accounting for gender and body weight. Conclusions: More than a quarter of obese children and adolescents meet the diagnostic criteria for EH in the Campania region in southern Italy. These obese boys and girls have an increased prevalence of insulin resistance and apparently an initial reduction in renal function compared with obese children and adolescents with normal BP.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kristina F Standeven ◽  
Angela M Carter ◽  
Anthony J Balmforth ◽  
Stephen B Wheatcroft ◽  
Nigel M Hooper ◽  
...  

Neprilysin (NEP) cleaves several bioactive peptides involved in the regulation of vascular function. In human microvascular endothelial cells, fatty acids and glucose increase NEP activity, and inhibition of NEP in animal studies results in increased insulin sensitivity, suggesting that NEP may be related to the metabolic syndrome. We tested this hypothesis in cell, animal and human based models. Microarray analysis of mRNA expression in differentiated human adipocytes (Affymetrix Human Genome U133 Plus 2.0 arrays) showed NEP expression to be an order of magnitude higher than the average gene signal, suggesting that human adipocytes express high endogenous levels of NEP mRNA. Real time PCR confirmed high levels of NEP mRNA in preadipocytes which increased 28 fold during differentiation and reached levels equivalent to the endogenous control, GAPDH, by 14 days. We created a diet induced model of obesity by feeding male C57BL/6J mice a high-fat diet, which resulted in decreased glucose tolerance and insulin resistance in obese mice. Plasma NEP levels measured after 15 weeks of feeding were significantly higher in obese mice (1642 [± 529]) pg/μl) compared to lean mice (820 [± 487] pg/μl) (p < 0.01). NEP levels increased 4- and 9-fold in epididymal and mesenteric fat in obese, compared to lean, mice. In a study of 318 healthy white European males, plasma NEP measured by activity assay was significantly higher in subjects with the metabolic syndrome (MetS) and levels increased progressively with increasing number of MetS components, being ~8-fold higher in those with 5 MetS components compared with those with none. NEP correlated with insulin, HOMA and BMI in all subjects. In conclusion, we have generated cell, murine and human data which suggest that NEP may have an important role in cardio-metabolic risk associated with insulin resistance, with the adipocyte as a major source of NEP. These findings indicate that NEP is a novel adipokine that links insulin resistance to vascular risk.


2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Saeid Golbidi ◽  
Ismail Laher

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Iván Ferraz-Amaro ◽  
Carlos González-Juanatey ◽  
Raquel López-Mejias ◽  
Leyre Riancho-Zarrabeitia ◽  
Miguel A. González-Gay

Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-αantagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jiyun Ahn ◽  
Min Young Um ◽  
Hyunjung Lee ◽  
Chang Hwa Jung ◽  
Seok Hyun Heo ◽  
...  

Eleutheroside E (EE), a principal component ofEleutherococcus senticosus(ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF-α-induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Dimitrios Papandreou ◽  
Mirey Karavetian ◽  
Zacharoula Karabouta ◽  
Eleni Andreou

Background. The aim of this study was to investigate the relationship between metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in obese children. One hundred and twenty-five subjects aged 11-12 years old participated in the study.Methods. Anthropometric and biochemical indices were measured, including lipid and liver profile, blood glucose, serum insulin, and liver ultrasound.Results. Forty-four children (58.6%) were found to have MS. Insulin resistance was present in 78 (62.4%) children. Patients with MS were more likely to have NAFLD (P<0.001). Children with NAFLD had significantly higher body mass index, waist circumference, triglycerides, fasting insulin, and lower high-density lipoprotein compared to patients with normal livers (P<0.001). Insulin resistance was significantly higher in children with NAFLD (P<0.001). Obese children presenting with MS were 3.01 (2.87–3.57,P<0.002) times more likely to develop NAFLD compared to those without metabolic syndrome after adjustment of cofounders.Conclusions. Obese children with MS have a higher risk of developing NAFLD. Weight management and early prevention should be the first line of treatment to prevent any possible health issues later on.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1115 ◽  
Author(s):  
Daxiang Li ◽  
Ruru Wang ◽  
Jinbao Huang ◽  
Qingshuang Cai ◽  
Chung S. Yang ◽  
...  

Cardiovascular diseases have overtaken cancers as the number one cause of death. Hypertension is the most dangerous factor linked to deaths caused by cardiovascular diseases. Many researchers have reported that tea has anti-hypertensive effects in animals and humans. The aim of this review is to update the information on the anti-hypertensive effects of tea in human interventions and animal studies, and to summarize the underlying mechanisms, based on ex-vivo tissue and cell culture data. During recent years, an increasing number of human population studies have confirmed the beneficial effects of tea on hypertension. However, the optimal dose has not yet been established owing to differences in the extent of hypertension, and complicated social and genetic backgrounds of populations. Therefore, further large-scale investigations with longer terms of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of hypertensive risk factors, and to determine differences in beneficial effects amongst diverse populations. Moreover, data from laboratory studies have shown that tea and its secondary metabolites have important roles in relaxing smooth muscle contraction, enhancing endothelial nitric oxide synthase activity, reducing vascular inflammation, inhibiting rennin activity, and anti-vascular oxidative stress. However, the exact molecular mechanisms of these activities remain to be elucidated.


2020 ◽  
Vol 21 (6) ◽  
pp. 2192 ◽  
Author(s):  
Forough Jahandideh ◽  
Jianping Wu

In addition to the regulation of blood pressure, the renin-angiotensin system (RAS) also plays a key role in the onset and development of insulin resistance, which is central to metabolic syndrome (MetS). Due to the interplay between RAS and insulin resistance, antihypertensive compounds may exert beneficial effects in the management of MetS. Food-derived bioactive peptides with RAS blocking properties can potentially improve adipose tissue dysfunction, glucose intolerance, and insulin resistance involved in the pathogenesis of MetS. This review discusses the pathophysiology of hypertension and the association between RAS and pathogenesis of the MetS. The effects of bioactive peptides with RAS modulating effects on other components of the MetS are discussed. While the in vivo reports on the effectiveness of antihypertensive peptides against MetS are encouraging, the exact mechanism by which these peptides infer their effects on glucose and lipid handling is mostly unknown. Therefore, careful design of experiments along with standardized physiological models to study the effect of antihypertensive peptides on insulin resistance and obesity could help to clarify this relationship.


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