Effect of long-term therapy with an oral contraceptive on some aspects of hepatic lipid metabolism in vitro

1975 ◽  
Vol 24 (17) ◽  
pp. 1583-1588 ◽  
Author(s):  
Ira Weinstein ◽  
Richard Belitsky ◽  
Susan Seedman ◽  
Melvin J. Fregly ◽  
Terry N. Thrasher
Keyword(s):  
Lipid Metabolism ◽  
Oral Contraceptive ◽  
Term Therapy ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Long Term Therapy

scholarly journals CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway

2020 ◽  
Vol 295 (50) ◽  
pp. 17310-17322
Author(s):  
Yann Deleye ◽  
Alexia Karen Cotte ◽  
Sarah Anissa Hannou ◽  
Nathalie Hennuyer ◽  
Lucie Bernard ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Lipid Droplet ◽  
Acid Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Hepatic Fatty Acid Oxidation

In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development, two pathologies associated with impaired hepatic lipid metabolism. Although p16 was recently shown to control hepatic glucose homeostasis, it is unknown whether p16 also controls hepatic lipid metabolism. Using a combination of in vivo and in vitro approaches, we found that p16 modulates fasting-induced hepatic fatty acid oxidation (FAO) and lipid droplet accumulation. In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism. These transcriptional changes led to increased FAO and were associated with enhanced activation of PPARα through a mechanism requiring the catalytic AMPKα2 subunit and SIRT1, two known activators of PPARα. By contrast, p16 overexpression was associated with triglyceride accumulation and increased lipid droplet numbers in vitro, and decreased ketogenesis and hepatic mitochondrial activity in vivo. Finally, gene expression analysis of liver samples from obese patients revealed a negative correlation between CDKN2A expression and PPARA and its target genes. Our findings demonstrate that p16 represses hepatic lipid catabolism during fasting and may thus participate in the preservation of metabolic flexibility.

Long-term imatinib therapy promotes bone formation in CML patients

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2538-2547 ◽  
Author(s):  
Stephen Fitter ◽  
Andrea L. Dewar ◽  
Panagiota Kostakis ◽  
L. Bik To ◽  
Timothy P. Hughes ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Imatinib Therapy ◽  
Term Therapy ◽  
Bone Homeostasis ◽  
Bone Biopsies ◽  
Long Term Therapy

Imatinib inhibits tyrosine kinases important in osteoclast (c-Fms) and osteoblast (platelet-derived growth factor receptor [PDGF-R], c-Abl) function, suggesting that long-term therapy may alter bone homeostasis. To investigate this question, we measured the trabecular bone volume (TBV) in iliac crest bone biopsies taken from chronic myeloid leukemia (CML) patients at diagnosis and again after 2 to 4 years of imatinib therapy. Half the patients (8 of 17) showed a substantive increase in TBV (> 2-fold), after imatinib therapy, with the TBV in the posttreatment biopsy typically surpassing the normal upper limit for the patient's age group. Imatinib-treated patients exhibited reduced serum calcium and phosphate levels with hypophosphatemia evident in 53% (9 of 17) of patients. In vitro, imatinib suppressed osteoblast proliferation and stimulated osteogenic gene expression and mineralized-matrix production by inhibiting PDGF receptor function. In PDGF-stimulated cultures, imatinib dose-dependently inhibited activation of Akt and Crk-L. Using pharmacologic inhibitors, inhibition of PI3-kinase/Akt activation promoted mineral formation, suggesting a possible molecular mechanism for the imatinib-mediated increase in TBV in vivo. Further investigation is required to determine whether the increase in TBV associated with imatinib therapy may represent a novel therapeutic avenue for the treatment of diseases that are characterized by generalized bone loss.

Long-term adjustment of hepatic lipid metabolism after chronic stress and the role of FGF21

2022 ◽  
Vol 1868 (1) ◽  
pp. 166286
Author(s):  
Matthias Dille ◽  
Aleksandra Nikolic ◽  
Natalie Wahlers ◽  
Pia Fahlbusch ◽  
Sylvia Jacob ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Chronic Stress ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Regulation effects of rosemary (Rosmarinus officinalis Linn.) on hepatic lipid metabolism in OA induced NAFLD rats

2019 ◽  
Vol 10 (11) ◽  
pp. 7356-7365 ◽  
Author(s):  
Si-Jian Wang ◽  
Qian Chen ◽  
Meng-Yang Liu ◽  
Hai-Yang Yu ◽  
Jing-Qi Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Rosmarinus Officinalis ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Regulate Lipid Metabolism ◽  
Effective Function

This paper first demonstrated that rosemary has an effective function to regulate lipid metabolism through the AMPK/SREBP1c signaling pathway in vivo and in vitro.

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