id:"swepub:oai:lup.lub.lu.se:4b440844-6cc2-4891-8a28-333a8bd1193a"
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04521naa a2200565 4500 | |
| 001 | oai:lup.lub.lu.se:4b440844-6cc2-4891-8a28-333a8bd1193a | |
| 003 | SwePub | |
| 008 | 221130s2022 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://lup.lub.lu.se/record/4b440844-6cc2-4891-8a28-333a8bd1193a2 URI |
| 024 | 7 | a https://doi.org/10.1016/j.jbc.2022.1023472 DOI |
| 040 | a (SwePub)lu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a art2 swepub-publicationtype |
| 072 | 7 | a ref2 swepub-contenttype |
| 100 | 1 | a Gupta, Abhisheku Ohio University4 aut |
| 245 | 1 0 | a Human CIDEC transgene improves lipid metabolism and protects against high-fat diet–induced glucose intolerance in mice |
| 264 | 1 | b Elsevier BV,c 2022 |
| 520 | a Cell death–inducing DNA fragmentation factor-like effector C (CIDEC) expression in adipose tissue positively correlates with insulin sensitivity in obese humans. Further, E186X, a single-nucleotide CIDEC variant is associated with lipodystrophy, hypertriglyceridemia, and insulin resistance. To establish the unknown mechanistic link between CIDEC and maintenance of systemic glucose homeostasis, we generated transgenic mouse models expressing CIDEC (Ad-CIDECtg) and CIDEC E186X variant (Ad-CIDECmut) transgene specifically in the adipose tissue. We found that Ad-CIDECtg but not Ad-CIDECmut mice were protected against high-fat diet-induced glucose intolerance. Furthermore, we revealed the role of CIDEC in lipid metabolism using transcriptomics and lipidomics. Serum triglycerides, cholesterol, and low-density lipoproteins were lower in high-fat diet-fed Ad-CIDECtg mice compared to their littermate controls. Mechanistically, we demonstrated that CIDEC regulates the enzymatic activity of adipose triglyceride lipase via interacting with its activator, CGI-58, to reduce free fatty acid release and lipotoxicity. In addition, we confirmed that CIDEC is indeed a vital regulator of lipolysis in adipose tissue of obese humans, and treatment with recombinant CIDEC decreased triglyceride breakdown in visceral human adipose tissue. Our study unravels a central pathway whereby adipocyte-specific CIDEC plays a pivotal role in regulating adipose lipid metabolism and whole-body glucose homeostasis. In summary, our findings identify human CIDEC as a potential ‘drug’ or a ‘druggable’ target to reverse obesity-induced lipotoxicity and glucose intolerance. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng |
| 653 | a CGI-58 | |
| 653 | a Cidec | |
| 653 | a diabetes | |
| 653 | a FSP27 | |
| 653 | a lipid droplets | |
| 653 | a lipids | |
| 653 | a metabolism | |
| 653 | a obesity | |
| 700 | 1 | a Balakrishnan, Bijinuu Ohio University4 aut |
| 700 | 1 | a Karki, Shakunu Boston University4 aut |
| 700 | 1 | a Slayton, Marku Ohio University4 aut |
| 700 | 1 | a Jash, Sukantau Brown University4 aut |
| 700 | 1 | a Banerjee, Sayaniu Brown University4 aut |
| 700 | 1 | a Grahn, Tan Hooi Minu Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematopoes och genterapi,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoiesis and Gene Therapy,Lund University Research Groups4 aut0 (Swepub:lu)med-snt |
| 700 | 1 | a Jambunathan, Srikarthikau Boston University4 aut |
| 700 | 1 | a Disney, Sarahu Ohio University4 aut |
| 700 | 1 | a Hussein, Hebaallahau Ohio University4 aut |
| 700 | 1 | a Kong, Dongu Boston Children's Hospital4 aut |
| 700 | 1 | a Lowell, Bradford B.u Harvard Medical School,Beth Israel Deaconess Medical Center4 aut |
| 700 | 1 | a Natarajan, Purushothamanu University of West Virginia4 aut |
| 700 | 1 | a Reddy, Umesh K.u University of West Virginia4 aut |
| 700 | 1 | a Gokce, Noyanu Boston University4 aut |
| 700 | 1 | a Sharma, Vishva M.u Ohio University4 aut |
| 700 | 1 | a Puri, Vishwajeetu Ohio University4 aut |
| 710 | 2 | a Ohio Universityb Boston University4 org |
| 773 | 0 | t Journal of Biological Chemistryd : Elsevier BVg 298:9q 298:9x 0021-9258 |
| 856 | 4 | u http://dx.doi.org/10.1016/j.jbc.2022.102347x freey FULLTEXT |
| 856 | 4 8 | u https://lup.lub.lu.se/record/4b440844-6cc2-4891-8a28-333a8bd1193a |
| 856 | 4 8 | u https://doi.org/10.1016/j.jbc.2022.102347 |
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