scholarly journals Ablation of Dihydroceramide Desaturase 1, a Therapeutic Target for the Treatment of Metabolic Diseases, Simultaneously Stimulates Anabolic and Catabolic Signaling

2013 ◽  
Vol 33 (11) ◽  
pp. 2353-2369 ◽  
Author(s):  
M. M. Siddique ◽  
Y. Li ◽  
L. Wang ◽  
J. Ching ◽  
M. Mal ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Metabolic Diseases ◽  
Dihydroceramide Desaturase ◽  
Dihydroceramide Desaturase 1

12,13-diHOME as a new therapeutic target for metabolic diseases

Life Sciences ◽  
2021 ◽  
pp. 120229
Author(s):  
Ana Paula Azevêdo Macêdo ◽  
Vitor Rosetto Muñoz ◽  
Dennys Esper Cintra ◽  
José Rodrigo Pauli
Keyword(s):  
Therapeutic Target ◽  
Metabolic Diseases

scholarly journals Update on FXR Biology: Promising Therapeutic Target?

2018 ◽  
Vol 19 (7) ◽  
pp. 2069 ◽  
Author(s):  
Chang Han
Keyword(s):  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Energy Status ◽  
Safety Issues ◽  
Attractive Therapeutic Target

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

Dihydroceramide-desaturase-1-mediated caspase 9 activation through ceramide plays a pivotal role in palmitic acid-induced HepG2 cell apoptosis

APOPTOSIS ◽  
2016 ◽  
Vol 21 (9) ◽  
pp. 1033-1044 ◽  
Author(s):  
Qun Zhu ◽  
Jianjun Yang ◽  
Rongping Zhu ◽  
Xin Jiang ◽  
Wanlian Li ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Hepg2 Cell ◽  
Cell Apoptosis ◽  
Pivotal Role ◽  
Caspase 9 ◽  
Dihydroceramide Desaturase ◽  
Dihydroceramide Desaturase 1

scholarly journals Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

2020 ◽  
Author(s):  
Rebecca Ward ◽  
Joanna J. Kaylor ◽  
Diego F. Cobice ◽  
Dionissia A. Pepe ◽  
Eoghan M. McGarrigle ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Bright Light ◽  
Immediate Early ◽  
Light Conditions ◽  
Photopic Vision ◽  
Wide Range ◽  
Dihydroceramide Desaturase ◽  
Cone Photopigments ◽  
Dihydroceramide Desaturase 1

AbstractCone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters (atRE) to 11-cis-retinol (11cROL) is mediated by the retinoid isomerohydrolase Rpe65. An alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, whereas emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaption displayed significantly attenuated immediate photopic vision concomitantly with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 minutes of light, early photopic vision recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde (9cRAL) supplementation. Genetic knockout of degs1 or retinaldehyde-binding protein 1b (rlbp1b) revealed that neither are required for photopic vision in zebrafish. Our findings define the molecular and temporal requirements of the non-photopic and photopic visual cycles for mediating vision in bright light.

scholarly journals The Logic of Carotid Body Connectivity to the Brain

Physiology ◽  
2019 ◽  
Vol 34 (4) ◽  
pp. 264-282 ◽  
Author(s):  
Tymoteusz Zera ◽  
Davi J. A. Moraes ◽  
Melina P. da Silva ◽  
James P. Fisher ◽  
Julian F. R. Paton
Keyword(s):  
Carotid Body ◽  
Therapeutic Target ◽  
Metabolic Diseases ◽  
Reflex Response ◽  
Differential Modulation ◽  
Glomus Cell ◽  
Distinct Component ◽  
Differential Control ◽  
The Brain

The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control of individual responses. We purport a remarkable correlation between phenotype of a chemosensory unit (glomus cell-sensory afferent) with a distinct component of the reflex response. This logic could permit differential modulation of distinct chemoreflex responses, a strategy ideal for therapeutic exploitation.

scholarly journals Gut Microbiota as a Prospective Therapeutic Target for Curcumin: A Review of Mutual Influence

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Wissam Zam
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Target ◽  
Intestinal Microflora ◽  
Metabolic Diseases ◽  
Mutual Influence ◽  
Ayurvedic Medicine ◽  
Potential Therapeutic Target ◽  
Pharmacological Activities ◽  
Turmeric Extract ◽  
Systemic Bioavailability

Background. Turmeric is a spice that has recently received much interest and has been widely used in Ayurvedic medicine. Turmeric products are diarylheptanoids and have been characterized as safe. They are termed as curcuminoids that consists essentially of three major compounds: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin is a lipophilic polyphenol that has poor systemic bioavailability and suffers from biotransformation by human intestinal microflora to yield different metabolites that are easily conjugated to glucuronides and sulfate O-conjugated derivatives. Recently, an increasing number of studies have indicated that dysbiosis is linked with many metabolic diseases, though gut microbiota could be a novel potential therapeutic target. Scope and Approach. Thus, it is suspected that curcumin and its derivatives exert direct regulative effects on the gut microbiota which could explain the paradox between curcumin’s poor systemic bioavailability and its widely reported pharmacological activities. Key Findings and Conclusions. This article summarizes a range of studies that highlight the interaction between curcumin and gut microbiota and considers opportunities for microbiome-targeting therapies using turmeric extract.

scholarly journals Delineating the Role of TRP Channels in Metabolic Disease (P10-083-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yan Qin Tan ◽  
Lai Kwok Leung
Keyword(s):  
Diabetes Mellitus ◽  
Western Blotting ◽  
Therapeutic Target ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Trp Channels ◽  
Maturation Process ◽  
Novel Therapeutic

Abstract Objectives The objective of the present study is to elucidate the role of Transient Receptor Potential (TRP) channels in the process of adipogenesis and diabetes mellitus, in hopes of getting more understanding of the role of TRP channels in the process as well as in hopes of discovering a novel therapeutic target against metabolic diseases. Methods The role of TRP channels in adipogenesis and diabetes mellitus was investigated by using in vivo (C57/BL6J mice) and in vitro (3T3-L1 cells). The expressions of TRP isoforms were studied by using RT-PCR and western blotting assay. TRP channels agonist and antagonist were used to study the role of TRP channels while fat accumulation in cells was visualized by Oil Red O staining. Intracellular calcium inflow was estimated by confocal microscopy. Results Among the TRP channels screened, the authors identified the differential expressions of TRPC isoforms by using in vivo model. The results were further confirmed by using western blotting analysis. The changes in expression suggested the importance of the specific isoforms in the adipogenesis process. The agonist-antagonist study illustrated that the treatment of TRPC antagonists induced the maturation process while TRPC agonist attenuated adipocyte differentiation of 3T3-L1 cells. Conclusions The present study serves to illustrate the role of TRP channels in adipocyte biology. In conclusion, the current study demonstrated that the TRPC isoforms have differential expression during the maturation process of fat. Further, the modulation of TRPC could affect the adipocyte differentiation of 3T3-L1 cells. The understanding of TRPC channels in adipocyte biology serves as a novel therapeutic target against metabolic diseases such as obesity and diabetes mellitus. Funding Sources The research is funded by The Chinese University of Hong Kong Direct Grant. Supporting Tables, Images and/or Graphs

Sign in / Sign up

Export Citation Format

Share Document