Untitled

Pacchioni, M.; Nicoletti, Cristian; Caminiti, Maurizio; Calori, Giliola; Curci, Vincenzo; Camisasca, R.; Pontiroli, Antonio E.

doi:10.1023/a:1005544009372

Cited by 38 publications

(14 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, there is a strong clinical association between type II diabetes plus obesity on the one hand and gallstone disease on the other (20). However, whether the increased gallstone formation was due to the diabetes or other complications associated with obesity has been somewhat controversial (21). Our studies demonstrating that CYP7A1 is increased in livers of diabetic mice support a direct association between diabetes and bile acid metabolism that could contribute directly to gallstone production independent of obesity.…”

Section: Discussionsupporting

confidence: 52%

PGC-1α Activates CYP7A1 and Bile Acid Biosynthesis

Shin

Campos

Gil

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cholesterol 7-␣-hydroxylase (CYP7A1) is the key enzyme that commits cholesterol to the neutral bile acid biosynthesis pathway and is highly regulated. In the current studies, we have uncovered a role for the transcriptional co-activator PGC-1␣ in CYP7A1 gene transcription. PGC-1␣ plays a vital role in adaptive thermogenesis in brown adipose tissue and stimulates genes important to mitochondrial function and oxidative metabolism. It is also involved in the activation of hepatic gluconeogenesic gene expression during fasting. Because the mRNA for CYP7A1 was also induced in mouse liver by fasting, we reasoned that PGC-1␣ might be an important co-activator for CYP7A1. Here we show that PGC-1␣ and CYP7A1 are also co-induced in livers of mice in response to streptozotocin induced diabetes. Additionally, infection of cultured HepG2 cells with a recombinant adenovirus expressing PGC-1␣ directly activates CYP7A1 gene expression and increases bile acid biosynthesis as well. Furthermore, we show that PGC-1␣ activates the CYP7A1 promoter directly in transient transfection assays in cultured cells. Thus, PGC-1␣ is a key activator of CYP7A1 and bile acid biosynthesis and is likely responsible for the fasting and diabetes dependent induction of CYP7A1. PGC-1␣ has already been shown to be a critical activator of several other oxidative processes including adaptive thermogenesis and fatty acid oxidation. Our studies provide further evidence of the fundamental role played by PGC-1␣ in oxidative metabolism and define PGC-1␣ as a link between diabetes and bile acid metabolism. The CYP7A11 enzyme converts cholesterol into 7-␣-hydroxycholesterol, which is the first specific intermediate in the neutral bile acid biosynthesis pathway in the liver (1). This is a crucial enzyme in mammalian cholesterol metabolism as diversion into the bile acid pathway is the main route for eliminating excess cholesterol from the body. Because of its key role in cholesterol metabolism, the CYP7A1 enzyme and its gene have been studied as an important model for dietary regulation for several years. These studies have revealed that there is a significant amount of regulation at the level of transcription initiation (2); however, post-transcriptional mechanisms for control also occur (1, 3).The CYP7A1 promoter has been extensively evaluated by several groups and the proximal regions of both the mouse and rat promoters contain two direct repeat type elements that bind several nuclear receptors, some of which are indicated in Fig. 1. There is also a binding site for the monomeric orphan receptor LRH-1 that overlaps the DR-1 element. The DR-4 is a target site for the nuclear receptor LXR, which confers positive regulation by cholesterol to the CYP7A1 promoter in mice and rats (2). However, the DR-4 is not conserved in the human gene which is not subject to feed forward regulation by cholesterol (4).CYP7A1 is also activated in livers of fasted mice (5). Similarly, the transcriptional co-activator PGC-1␣ is induced by fasting in liver where it activates transcrip...

show abstract

Section: Discussionsupporting

confidence: 52%

PGC-1α Activates CYP7A1 and Bile Acid Biosynthesis

Shin

Campos

Gil

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The established risk factors for gallstone disease in the previous studies were old age, obesity and female,4,5,6) as well as pregnancy, oral contraceptives, alcohol, smoking, and diabetes 7,8,9). In this study, age and BMI in the gallstone group was higher than the non-gallstone group (Table 1).…”

Section: Discussionsupporting

confidence: 45%

“…The established risk factors which cause cholesterol stones are old age, female, obesity4,5,6) as well as pregnancy, oral contraceptives, alcohol, smoking, and diabetes 7,8,9). Amongst these risk factors, age, obesity, smoking, and diabetes are the risk factors for atherosclerosis,10,11,12,13) hence the proposed relationship between gallstones and atherosclerosis.…”

Section: Introductionmentioning

confidence: 97%

Gallstones are Associated with Intima-Media Thickness of Common Carotid Arteries in Men

et al. 2014

View full text Add to dashboard Cite

BackgroundThe prevalence of gallstone disease is increasing in Korea. Gallstone disease and atherosclerosis share common risk factors. Ultrasonographic carotid intima-media thickness is an independent predictor of atherosclerosis. We measured the carotid intima-media thickness among men who had gallstones to establish the association between atherosclerosis and gallstones.MethodsA total of 330 men who visited the health promotion center of the IS Hallym Hospital from January 2011 to July 2012 were recruited. Both abdomen and carotid ultrasonographies were performed. Demographic, anthropometric, and biochemical data were collected.ResultsThe prevalence of gallstones was 6.6%. The carotid intima-media thickness, age, and body mass index were higher in subjects with gallstones (P < 0.05 for all). After Pearson correlation analysis, gallstone, age, body mass index, and fasting blood sugar were significantly associated with carotid intima-media thickness. A statistically positive association between gallstone and carotid intima-media thickness was demonstrated in a multivariate analysis adjusted for age, body mass index, and fasting blood sugar.ConclusionCarotid intima-media thickness is higher in male subjects with gallstones, indicating that they are at greater risk for atherosclerosis.

show abstract

“…DM is identified as a risk factor in the presence of other risk factors like obesity and family history of GS disease [40]. Moreover in Western population obesity is the strongest risk factor for GS even in patients with DM [41]. …”

Section: Discussionmentioning

confidence: 99%

Can the type of gallstones be predicted with known possible risk factors?: a comparison between mixed cholesterol and black pigment stones

et al. 2014

View full text Add to dashboard Cite

BackgroundPathogenesis of gallstones (GS) is multifactorial and multiple genetic and environmental factors have been identified in different populations for different types of GS with varying prevalence. However the role of the each aetiological factor on the formation of mixed cholesterol and black pigment GS has not being addressed adequately. Hence in this study we attempted to compare known possible risk factors for mixed cholesterol and black pigment GS among two groups of patients with two types of GS.MethodsThe study was done on a cohort of patients with symptomatic GS admitted to the Teaching Hospital Peradeniya, Sri Lanka over a period of 18 months. Clinical and epidemiological data and physical parameters of the patients were recorded and surgically removed GS were analyzed chemically and physically to identify the type of GS. In addition lipid profile was done in all the patients with normal serum bilirubin levels.ResultsA total of 86 patients were included in the study. Mixed cholesterol GS was significantly common among females than males (χ2 test, p = 0.029). Mixed cholesterol GS was commonly seen among patients belonging to Moor ethnicity (χ2 test, p = 0.009). Majority of patients with mixed cholesterol GS had body mass index above 25 kg/m2 (χ2 test, p = 0.018). Black pigment GS were significantly common among patients with type II diabetes mellitus (Fisher’s exact test, p = 0.035). Further all the patients with chronic haemolytic anaemia and alcoholic cirrhosis had black pigment GS. Age, family history, Fasting Blood Glucose, dyslipidaemia, lipid profile, parity and use of oral contraceptive pills in females, smoking and alcohol intake in males did not differ significantly among patients in the two groups.ConclusionGender, ethnicity and body mass index can be used to predict the formation of mixed cholesterol GS and black pigment GS.

show abstract

Untitled

Cited by 38 publications

References 27 publications

PGC-1α Activates CYP7A1 and Bile Acid Biosynthesis

PGC-1α Activates CYP7A1 and Bile Acid Biosynthesis

Gallstones are Associated with Intima-Media Thickness of Common Carotid Arteries in Men

Can the type of gallstones be predicted with known possible risk factors?: a comparison between mixed cholesterol and black pigment stones

Contact Info

Product

Resources

About