Metabolic Comparison of One-Anastomosis Gastric Bypass, Single-Anastomosis Duodenal-Switch, Roux-en-Y Gastric Bypass, and Vertical Sleeve Gastrectomy in Rat

Background One-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal switch (SADS) have become increasingly popular weight loss strategies. However, data directly comparing the effectiveness of these procedures with Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (SG) are limited. Objectives To examine the metabolic outcomes of OAGB, SADS, RYGB, and SG in a controlled rodent model. Setting Academic research laboratory, United States. Methods Surgeries were performed in diet-induced obese Long-Evans rats, and metabolic outcomes were monitored before and for 15 weeks after surgery. Results All bariatric procedures induced weight loss compared with sham that lasted throughout the course of the study. The highest percent fat loss occurred after OAGB and RYGB. All bariatric procedures had improved glucose dynamics associated with an increase in insulin (notably OAGB and SADS) and/or glucagon-like protein-1 secretion. Circulating cholesterol was reduced in OAGB, SG, and RYGB. OAGB and SG additionally decreased circulating triglycerides. Liver triglycerides were most profoundly reduced after OAGB and RYGB. Circulating iron levels were decreased in all surgical groups, associated with a decreased hematocrit value and increased reticulocyte count. The fecal microbiome communities of OAGB, SADS, and RYGB were significantly altered; however, SG exhibited no change in microbiome diversity or composition. Conclusions These data support the use of the rat for modeling bariatric surgical procedures and highlight the ability of the OAGB to meet or exceed the metabolic improvements of RYGB. These data point to the likelihood that each surgery accomplishes metabolic improvements through both overlapping and distinct mechanisms and warrants further research

Maternal hepatic growth response to pregnancy in the mouse

Pregnancy is characterized by physiological adjustments in the maternal compartment. In this investigation, the influence of pregnancy on maternal liver was examined in CD-1 mice. Dramatic changes were observed in the size of the maternal liver during pregnancy. Livers doubled in weight from the non-pregnant state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a physiological event of liver growth confirmed by DNA content increase and detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was initiated following implantation and peaked at parturition. The expression and/or activities of key genes known to regulate liver regeneration, a phenomenon of liver growth compensatory to liver mass loss, were investigated. The results showed that pregnancy-dependent liver growth was associated with interleukin (IL)-6, tumor necrosis factor α, c-Jun and IL-1β, but independent of hepatocyte growth factor, fibroblast growth factor 1, tumor necrosis factor receptor 1, constitutive androstane receptor and pregnane X receptor. Furthermore, maternal liver growth was associated with the activation of hepatic signal transducer and activator of transcription 3, β-catenin and epidermal growth factor receptor, but pregnancy did not activate hepatic c-Met. The findings suggest that the molecular mechanisms regulating pregnancy-induced liver growth and injury-induced liver regeneration exhibit overlapping features but are not identical. In summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic growth response driven by hepatocyte proliferation and size increase

Platelets Strongly Induce Hepatocyte Proliferation with IGF-1 and HGF In Vitro

Background. It is well known that platelets have athrombotic effect. However, platelets play an importantrole not only in hemostasis but also in woundhealing and tissue regeneration. Platelets have beenreported to accumulate in the liver and promote liverregeneration after an extended hepatectomy, but themechanism is unclear. The present study was designedto clarify the mechanism by which plateletshave a direct proliferative effect on hepatocytes invitro.Materials and methods. Hepatocytes obtained frommale BALB/c mice by collagenase digestion and immortalizedhepatocytes (TLR2) were used. To elucidatethe mechanism of the proliferative effect of platelets,DNA synthesis of hepatocytes was measuredunder various conditions and the related cellular signalswere analyzed. Chromatographic analysis wasalso performed to clarify which elements of plateletshave mitogenic activity.Results. DNA synthesis significantly increased in thehepatocytes cultured with platelets (P < 0.001). However,when the platelets and hepatocytes were separated,the platelets did not have a proliferative effect.Whole disrupted platelets, the supernatant fraction,and fresh isolated platelets had a similar proliferativeeffect, while the membrane fraction did not. After theaddition of platelets, both Akt and extracellularsignal-regulated kinases ERK1/2 were activated, butextracellular signal-regulated kinase STAT3 was not activated. Some mitogenic fractions were obtainedfrom the platelet extracts by gel exclusion chromatography;the fractions were rich in hepatocyte growthfactor and IGF-1.Conclusions. Direct contact between platelets andhepatocytes was necessary for the proliferative effect.The direct contact initiated signal transduction involvedin growth factor activation. Hepatocyte growthfactor, vascular endothelial growth factor, and insulin-like growth factor-1, rather than platelet-derivedgrowth factor, mainly contributed to hepatocyteproliferation

Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight‐loss‐independent manner

ObjectiveOur objective was to investigate the role of bile acids in hepatic steatosis reduction after vertical sleeve gastrectomy (VSG).Design and methodsHigh fat diet (HFD)-induced obese C57Bl/6 mice were randomized to VSG, Sham operation (Sham), Sham operation with pair feeding to VSG (Sham-PF), or nonsurgical controls (Naïve). All mice were on HFD until sacrifice. Mice were observed postsurgery and data for body weight, body composition, metabolic parameters, serum bile acid level and composition were collected. Further hepatic gene expression by mRNA-seq and RT-PCR analysis was assessed.ResultsVSG and Sham-PF mice lost equal weight postsurgery while VSG mice had the lowest hepatic triglyceride content at sacrifice. The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss. Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid. These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes.ConclusionVSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone. VSG surgery increases serum bile acids that correlate with weight lost postsurgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis