Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling.
Eighty percent of patients who receive bariatric surgery are women, yet the majority of preclinical studies are in male rodents. Because sex differences drive hepatic gene expression and overall lipid metabolism, we sought to determine whether sex differences were also apparent in these endpoints in response to bariatric surgery.



Two cohorts of age-matched virgin male and female Long-Evans rats were placed on a high fat diet for 3 weeks and then received either Sham or vertical sleeve gastrectomy (VSG), a surgery which resects 80% of the stomach with no intestinal rearrangement.



Each sex exhibited significantly decreased body weight due to a reduction in fat mass relative to Sham controls (p< 0.05). Microarray and follow-up qPCR on liver revealed striking sex differences in gene expression after VSG that reflected a down-regulation of hepatic lipid metabolism and an up-regulation of hepatic inflammatory pathways in females vs. males after VSG. While the males had a significant reduction in hepatic lipids after VSG, there was no reduction in females.Ad lib-fed and fasting circulating triglycerides, and postprandial chylomicron production were significantly lower in VSG relative to Sham animals of both sexes (p< 0.01). However, hepatic VLDL production, highest in sham-operated females, was significantly reduced by VSG in females but not males.



Taken together, although both males and females lose weight and improve plasma lipids, there are large-scale sex differences in hepatic gene expression and consequently hepatic lipid metabolism after VSG.
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS USA.
Bernadette E
BE
Grayson
Divsion de Investigacion, Facultad de Medicina, Universidad Nacional Autónoma de México and Laboratorio de Enfermedades Metabólicas Obesidad y Diabetes, Hospital Infantil de México "Federico Gómez", Mexico, Mexico.
Ruth
R
Gutierrez-Aguilar
Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio USA.
Joyce E
JE
Sorrell
Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio USA.
Emily K
EK
Matter
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio USA.
Michelle R
MR
Adams
Department of Pathology, University of Cincinnati, Cincinnati, Ohio USA.
Philip
P
Howles
Bioinformatics Core, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio USA.
Rebekah
R
Karns
Department of Surgery, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 USA.
Randy J
RJ
Seeley
Department of Surgery, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 USA.
Darleen A
DA
Sandoval
D000818:Animals; D050110:Bariatric Surgery; D005260:Female; D005743:Gastrectomy; D015870:Gene Expression; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D015431:Weight Loss
Bariatric surgery; Liver; Sex difference; Triglycerides; Vertical sleeve gastrectomy