title: High Fat Diets Sex-Specifically Affect the Renal Transcriptome and Program Obesity, Kidney Injury, and Hypertension in the Offspring.
abstract: Obesity and related disorders have increased concurrently with an increased consumption of saturated fatty acids. We examined whether post-weaning high fat (HF) diet would exacerbate offspring vulnerability to maternal HF-induced programmed hypertension and kidney disease sex-specifically, with a focus on the kidney. Next, we aimed to elucidate the gene-diet interactions that contribute to maternal HF-induced renal programming using the next generation RNA sequencing (NGS) technology. Female Sprague-Dawley rats received either a normal diet (ND) or HF diet (D12331, Research Diets) for five weeks before the delivery. The offspring of both sexes were put on either the ND or HF diet from weaning to six months of age, resulting in four groups of each sex (maternal diet/post-weaning diet;n= 5-7/group): ND/ND, ND/HF, HF/ND, and HF/HF. Post-weaning HF diet increased bodyweights of both ND/HF and HF/HF animals from three to six months only in males. Post-weaning HF diet increased systolic blood pressure in male and female offspring, irrespective of whether they were exposed to maternal HF or not. Male HF/HF offspring showed greater degrees of glomerular and tubular injury compared to the ND/ND group. Our NGS data showed that maternal HF diet significantly altered renal transcriptome with female offspring being more HF-sensitive. HF diet induced hypertension and renal injury are associated with oxidative stress, activation of renin-angiotensin system, and dysregulated sodium transporters and circadian clock. Post-weaning HF diet sex-specifically exacerbates the development of obesity, kidney injury, but not hypertension programmed by maternal HF intake. Better understanding of the sex-dependent mechanisms that underlie HF-induced renal programming will help develop a novel personalized dietary intervention to prevent obesity and related disorders.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.|Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. ray.sheen@gmail.com.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. yuu2004taiwan@yahoo.com.tw.
authors.forename: Jiunn-Ming
authors.initials: JM
authors.lastname: Sheen
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tmm@cgmh.org.tw.
authors.forename: Hong-Ren
authors.initials: HR
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. charllysc@cgmh.org.tw.
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. litung.huang@gmail.com.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. lyu015ster@gmail.com.
authors.forename: Ching-Chou
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. nick@cgmh.org.tw.|Department of Traditional Chinese Medicine, Chang Gung University, Linkow 244, Taiwan. nick@cgmh.org.tw.
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. chien_ning_hsu@hotmail.com.|School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chien_ning_hsu@hotmail.com.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Hsu
mesh_terms: D000818:Animals; D021081:Chronobiology Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D057906:Circadian Clocks; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012737:Sex Factors; D059467:Transcriptome; D014886:Weaning; D015430:Weight Gain
keywords: clock gene; developmental origins of health and disease (DOHaD); high-fat diet; hypertension; kidney disease; next generation sequencing; nitric oxide; oxidative stress; renin-angiotensin system