Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

2009 ◽  
Vol 89 (1) ◽  
pp. 147-191 ◽  
Author(s):  
Philippe Lefebvre ◽  
Bertrand Cariou ◽  
Fleur Lien ◽  
Folkert Kuipers ◽  
Bart Staels
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Bile Acids ◽  
Disease Risk ◽  
Critical Role ◽  
Elevated Serum ◽  
Farnesoid X Receptor ◽  
The Metabolic Syndrome ◽  
Increased Risk

The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be defined as a cluster of cardiovascular disease risk factors including visceral obesity, insulin resistance, dyslipidemia, increased blood pressure, and hypercoagulability. The farnesoid X receptor (FXR) belongs to the superfamily of ligand-activated nuclear receptor transcription factors. FXR is activated by bile acids, and FXR-deficient ( FXR−/−) mice display elevated serum levels of triglycerides and high-density lipoprotein cholesterol, demonstrating a critical role of FXR in lipid metabolism. In an opposite manner, activation of FXR by bile acids (BAs) or nonsteroidal synthetic FXR agonists lowers plasma triglycerides by a mechanism that may involve the repression of hepatic SREBP-1c expression and/or the modulation of glucose-induced lipogenic genes. A cross-talk between BA and glucose metabolism was recently identified, implicating both FXR-dependent and FXR-independent pathways. The first indication for a potential role of FXR in diabetes came from the observation that hepatic FXR expression is reduced in animal models of diabetes. While FXR−/−mice display both impaired glucose tolerance and decreased insulin sensitivity, activation of FXR improves hyperglycemia and dyslipidemia in vivo in diabetic mice. Finally, a recent report also indicates that BA may regulate energy expenditure in a FXR-independent manner in mice, via activation of the G protein-coupled receptor TGR5. Taken together, these findings suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes.

scholarly journals Dysfunctional Endothelial Progenitor Cells in Metabolic Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Sridevi Devaraj ◽  
Ishwarlal Jialal
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Endothelial Dysfunction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Angiotensin Receptor Blockers ◽  
Endothelial Progenitor ◽  
The Metabolic Syndrome ◽  
Increased Risk

The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34+KDR+phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS.

Abstract P189: Associations between Lactation and Maternal Measures of Total and Regional Adiposity 15 Years Postpartum: Results from the Study of Women’s Health Across the Nation

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Candace K McClure ◽  
Christina M Shay ◽  
Ping G Tepper ◽  
Molly B Conroy ◽  
Barbara Sternfeld ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Women’S Health ◽  
Women's Health ◽  
Menopausal Status ◽  
Lower Leg ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Regional Adiposity

Objective: It has been reported that mothers who do not breastfeed are at an increased risk of T2DM, metabolic syndrome, and CVD. We hypothesize that lactation may influence cardio-metabolic risk by altering maternal body composition. We examined the extent to which lactation was associated with regional and total adiposity in a sample of US women 15 years after their last birth. Study Design : Cross-sectional analysis of data provided by 1,268 women aged 45-58 who enrolled in the Study of Women’s Health Across the Nation (1996 -1997). Adiposity was assessed using dual-energy X-ray absorptiometry. History of lactation was self-reported and categorized into three groups: mothers who breastfed for ≥3 months after every birth, those who discontinued lactation within 3 months of some births, and those who never breastfed. Results: Compared with mothers who breastfed after every birth for at least 3 months, mothers who never breastfed had 0.87 kg greater trunk fat mass (FM), 1.3% greater % trunk FM, 1.3% lower % leg FM, and 0.075 greater trunk to leg FM ratio after adjustment for age, parity, height, years since last birth, race/ethnicity, socioeconomic, lifestyle, psychological, and family history variables, maximum gestational weight gain, and menopausal status. After additional adjustment for current BMI, women who never breastfed had 0.40 kg greater trunk FM and 0.053 greater trunk to leg FM ratio than mothers who breastfed every child for ≥3 months. Similarly, mothers who discontinued lactation within 3 months of some births had 0.28 kg greater trunk FM and 0.87% lower % leg FM than mothers who consistently breastfed. Conclusion : Women who did not breastfeed for at least 3 months after every birth exhibit less favorable body fat distributions 15 years postpartum. These results provide a potential physiologic basis for prior findings that women who do not breastfeed their children face increased risk of diabetes, the metabolic syndrome, and cardiovascular disease. Given existing disparities in rates of lactation, obesity and CVD, these findings have great clinical relevance and suggest the need for targeted lactation support for women at risk of cardiovascular disease.

scholarly journals Reversal Rate of Clustering of Cardiovascular Disease Risk Factors of Metabolic Syndrome in the General Population: The Niigata Preventive Medicine Study

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Shinsuke Okada ◽  
Akiko Suzuki ◽  
Hiroshi Watanabe ◽  
Toru Watanabe ◽  
Yoshifusa Aizawa
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Disease Risk ◽  
Fasting Blood Glucose ◽  
Reversal Rate ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
The Metabolic Syndrome

The reversal rate from clustering of cardiovascular disease (CVD) risk factors—components of the metabolic syndrome (MetS) is not known.Methods and Results. Among 35,534 subjects who received the annual health examinations at the NiigataHealth Foundation (Niigata, Japan), 4,911 subjects had clustering of 3 or more of the following CVD risk factors: (1) body mass index (BMI) ≥25 Kg/m2, (2) blood pressure ≥130 mm Hg in systolic and/or ≥85 mm Hg in diastolic, (3) triglycerides ≥150 mg/dL, (4) high-density lipoprotein cholesterol ≤40 mg/dL in men, ≤50 mg/dL in women, and (5) fasting blood glucose ≥100 mg/dL. After 5 years 1,929 subjects had a reversal of clustering (39.4%). A reversal occurred more often in males. The subjects with a reversal of clustering had milder level of each risk factor and a smaller number of risk factors, while BMI was associated with the least chance of a reversal.Conclusion. We concluded that a reversal of clustering CVD risk factors is possible in 4/10 subjects over a 5-year period by habitual or medical interventions. Gender and each CVD risk factor affected the reversal rate adversely, and BMI was associated with the least chance of a reversal.

scholarly journals Modern fat technology: what is the potential for heart health?

2005 ◽  
Vol 64 (3) ◽  
pp. 379-386 ◽  
Author(s):  
J. E. Upritchard ◽  
M. J. Zeelenberg ◽  
H. Huizinga ◽  
P. M. Verschuren ◽  
E. A. Trautwein
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Disease Risk ◽  
Saturated Fatty Acids ◽  
Saturated Fat ◽  
Blood Cholesterol ◽  
Medical Community ◽  
The Metabolic Syndrome ◽  
Increased Risk

Saturated andtrans-fatty acids raise total cholesterol and LDL-cholesterol and are known to increase the risk of CHD, while dietary unsaturated fatty acids play important roles in maintaining cardiovascular health. Replacing saturated fats with unsaturated fats in the diet often involves many complex dietary changes. Modifying the composition of foods high in saturated fat, particularly those foods that are consumed daily, can help individuals to meet the nutritional targets for reducing the risk of CHD. In the 1960s the Dutch medical community approached Unilever about the technical feasibility of producing margarine with a high-PUFA and low-saturated fatty acid composition. Margarine is an emulsion of water in liquid oil that is stabilised by a network of fat crystals. In-depth expertise of fat crystallisation processes allowed Unilever scientists to use a minimum of solid fat (saturated fatty acids) to structure a maximum level of PUFA-rich liquid oil, thus developing the first blood-cholesterol-lowering product, Becel. Over the years the composition of this spread has been modified to reflect new scientific findings and recommendations. The present paper will briefly review the developments in fat technology that have made these improvements possible. Unilever produces spreads that are low in total fat and saturated fat, virtually free oftrans-fatty acids and with levels ofn-3 andn-6 PUFA that are in line with the latest dietary recommendations for the prevention of CHD. Individuals with the metabolic syndrome have a 2–4-fold increased risk of developing CHD; therefore, these spreads could make a contribution to CHD prevention in this group. In addition, for individuals with the metabolic syndrome the spreads could be further modified to address their unique dyslipidaemia, i.e. elevated blood triacylglycerols and low HDL-cholesterol. Research conducted in the LIPGENE study and other dietary intervention studies will deliver the scientific evidence to justify further modifications in the composition of spreads that are healthy for the heart disease risk factors associated with the metabolic syndrome.

scholarly journals Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1653
Author(s):  
Sze Wa Chan ◽  
Brian Tomlinson
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Vision Loss ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiovascular Complications ◽  
Increased Risk ◽  
Potential Benefits

Metabolic syndrome is a cluster of interrelated conditions that is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Oxidative stress may impair normal physiological functions, leading to various illnesses. T2DM is considered to be associated with increased oxidative stress, inflammation, and dyslipidemia, which may play a significant role in the development of cardiovascular complications, cancer and vision loss through cataracts and retinopathy. While conventional therapies are a cornerstone for the management of the major risk factors of metabolic syndrome, increasing antioxidant defense by increasing intake of antioxidant-rich foods may improve long term prospects in CVD, obesity and T2DM. Bilberry (Vaccinium myrtillus L.) is one of the richest natural sources of anthocyanins which give berries their red/purple/blue coloration. Anthocyanins are powerful antioxidants and are reported to play an important role in the prevention of metabolic disease and CVD as well as cancer and other conditions. This review focuses on the potential effects of bilberry supplementation on metabolic and cardiovascular risk factors. Although there is evidence to support the use of bilberry supplementation as part of a healthy diet, the potential benefits from the use of bilberry supplementation in patients with T2DM or CVD needs to be clarified in large clinical trials.

scholarly journals Variations in Adipokine GenesAdipoQ,Lep, andLepRAre Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jennifer Emily Enns ◽  
Carla G. Taylor ◽  
Peter Zahradka
Keyword(s):  
Metabolic Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Disease Risk ◽  
Critical Role ◽  
Nucleotide Polymorphisms ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome ◽  
Susceptible Populations

Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

scholarly journals Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy + Apoe −/− mouse model of the metabolic syndrome

Diabetologia ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 2660-2668 ◽  
Author(s):  
H. G. Martinez ◽  
M. P. Quinones ◽  
F. Jimenez ◽  
C. A. Estrada ◽  
K. Clark ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mouse Model ◽  
Critical Role ◽  
The Metabolic Syndrome ◽  
Apoe Mouse
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