title: Enhanced thermogenic program by non-viral delivery of combinatory browning genes to treat diet-induced obesity in mice.
abstract: Thermogenic program (also known as browning) is a promising and attractive anti-obesity approach. Islet amyloid polypeptide (IAPP) and irisin have emerged as potential browning hormones that hold high potential to treat obesity. Here, we have constructed a dual browning gene system containing both IAPP and irisin (derived from fibronectin type III domain containing 5; FNDC5) combined with 2A and furin self-cleavage sites. Intraperitoneal administration of the construct complexed with a linear polyethylenimine into diet-induced obese mice demonstrated the elevation of anti-obesogenic effects characterized as the decreased body weight, adiposity, and levels of glucose and insulin. In addition, the construct delivery increased energy expenditure and the expression of core molecular determinants associated with browning. The additional advantages of the dual browning gene construct delivery compared to both single gene construct delivery and dual peptide delivery can be emphasized on efficacy and practicability. Hence, we have concluded that dual browning gene delivery makes it therapeutically attractive for diet-induced obesity treatment.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Hongsuk
authors.initials: H
authors.lastname: Park
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Sungpil
authors.initials: S
authors.lastname: Cho
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Margit M
authors.initials: MM
authors.lastname: Janat-Amsbury
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Utah-Inha Drug Delivery Systems and Advanced Therapeutics Research Center, Incheon, Republic of Korea. Electronic address: you.bae@utah.edu.
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D050154:Adiposity; D000284:Administration, Oral; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002151:Calorimetry; D059305:Diet, High-Fat; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics*; D045683:Furin / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics* / Q000628:therapy*; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry; D022722:Thermogenesis / Q000235:genetics*
chemical_list: C571428:FNDC5 protein, mouse; D005353:Fibronectins; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D011094:Polyethyleneimine; D045683:Furin
keywords: Dual browning gene construct; FNDC5; IAPP; Irisin; Obesity; Thermogenic program