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A Longer Biliopancreatic Limb and Shorter Common Channel Enhance Weight Loss But May Have Harmful Effects in Mouse Models of Roux-en-Y Gastric Bypass
Lau, Raymond; Stevenson, Matthew; Tirumalasetty, Munichandra Babu; Lee, Jenny; Hall, Christopher; Miao, Qing; Brathwaite, Collin; Ragolia, Louis
BACKGROUND:RYGB consists of the Roux limb (RL), the biliopancreatic limb (BPL), and the common channel (CC). There is no consensus on the optimal limb lengths. METHODS:Using a mouse model of RYGB, 30 diet-induced obese mice were divided into two groups with varying BPL and CC lengths: a standard BPL with a long CC (RYGB S) and a long BPL with a short CC (RYGB L). Additionally, 9 age-matched, lean control mice (LC) were also included in this study. RESULTS:RYGB S had limb lengths of RL = 17%, BPL = 24%, and CC = 59%. RYGB L had limb lengths of RL = 17%, BPL = 32%, and CC = 51%. RYGB S and RYGB L had 67% and 40% survival, respectively. Mortality in RYGB L included more instances where the cause of death was not apparent. RYGB L demonstrated greater weight loss, lower energy expenditure, and lower heart mass as compared to RYGB S. Both RYGB groups had lower epidydimal fat mass, spleen mass, and bone mineral density compared to LC. RYGB L had a lower heart mass than RYGB S and LC. While the relative abundance of Eubacterium was lower in RYGB L than in RYGB S, no other gut microbiota differences were observed. CONCLUSIONS:A longer BPL with a shorter CC induces greater weight loss but may lead to adverse effects, including lower heart mass, reduced bone density, and deaths with unclear causes.
PMID: 39516446
ISSN: 1708-0428
CID: 5752272
Correction: A Longer Biliopancreatic Limb and Shorter Common Channel Enhance Weight Loss But May Have Harmful Effects in Mouse Models of Roux-en-Y Gastric Bypass
Lau, Raymond; Stevenson, Matthew; Tirumalasetty, Munichandra Babu; Lee, Jenny; Hall, Christopher; Miao, Qing; Brathwaite, Collin; Ragolia, Louis
PMID: 39612057
ISSN: 1708-0428
CID: 5780012
Beyond Measure: Navigating the Complexities of Limb Length Optimization in Roux-en-Y Gastric Bypass Surgery [Letter]
Stevenson, Matthew; Lau, Raymond; Brathwaite, Collin E M; Ragolia, Louis
PMID: 38743181
ISSN: 1708-0428
CID: 5732602
The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice
Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A E; Park, Christopher Y; Schlamp, Florencia; Heffron, Sean P; Fisher, Edward A; Brathwaite, Collin; Ragolia, Louis
PURPOSE/OBJECTIVE:Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. METHODS:A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8 weeks. RESULTS:After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. CONCLUSION/CONCLUSIONS:Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk.
PMID: 38191966
ISSN: 1708-0428
CID: 5707802
Correction: The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice
Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A E; Park, Christopher Y; Schlamp, Florencia; Heffron, Sean P; Fisher, Edward A; Brathwaite, Collin; Ragolia, Louis
PMID: 38236349
ISSN: 1708-0428
CID: 5737482
Microsomal triglyceride transfer protein regulates intracellular lipolysis in adipocytes independent of its lipid transfer activity
Rajan, Sujith; Hofer, Peter; Christiano, Amanda; Stevenson, Matthew; Ragolia, Louis; Villa-Cuesta, Eugenia; Fried, Susan K; Lau, Raymond; Braithwaite, Collin; Zechner, Rudolf; Schwartz, Gary J; Hussain, M Mahmood
BACKGROUND:The triglyceride (TG) transfer activity of microsomal triglyceride transfer protein (MTP) is essential for lipoprotein assembly in the liver and intestine; however, its function in adipose tissue, which does not assemble lipoproteins, is unknown. Here we have elucidated the function of MTP in adipocytes. APPROACH AND RESULTS/RESULTS:mice maintained higher body temperature by mobilizing more fatty acids. Biochemical studies indicated that MTP deficiency de-repressed adipose triglyceride lipase (ATGL) activity and increased TG lipolysis. Both wild type MTP and mutant MTP deficient in TG transfer activity interacted with and inhibited ATGL activity. Thus, the TG transfer activity of MTP is not required for ATGL inhibition. C-terminally truncated ATGL that retains its lipase activity interacted less efficiently than full-length ATGL. CONCLUSION/CONCLUSIONS:Our findings demonstrate that adipose-specific MTP deficiency increases ATGL-mediated TG lipolysis and enhances energy expenditure, thereby resisting diet-induced obesity. We speculate that the regulatory function of MTP involving protein-protein interactions might have evolved before the acquisition of TG transfer activity in vertebrates. Adipose-specific inhibition of MTP-ATGL interactions may ameliorate obesity while avoiding the adverse effects associated with inhibition of the lipid transfer activity of MTP.
PMID: 36228741
ISSN: 1532-8600
CID: 5352142
Reversal of NAFLD After VSG Is Independent of Weight-Loss but RYGB Offers More Efficacy When Maintained on a High-Fat Diet
Srivastava, Ankita; Stevenson, Matthew; Lee, Jenny; Hall, Christopher; Palaia, Thomas; Zhao, Chaohui Lisa; Lau, Raymond; Brathwaite, Collin; Ragolia, Louis
PURPOSE/OBJECTIVE:Bariatric surgery is emerging as an effective treatment for obesity and the metabolic syndrome. Recently, we demonstrated that Roux-en-Y gastric bypass (RYGB), but not vertical sleeve gastrectomy (VSG), resulted in improvements to white adipose physiology and enhanced brown adipose functioning. Since beneficial alterations to liver health are also expected after bariatric surgery, comparing the post-operative effects of RYGB and VSG on liver physiology is essential to their application in the treatment of non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS/METHODS:The effects of RYGB and VSG on liver physiology were compared using diet induced mouse model of obesity. High-fat diet (HFD) was administered for 12Â weeks after surgery and alterations to liver physiology were assessed. RESULTS:Both RYGB and VSG showed decreased liver weight as well as reductions to hepatic cholesterol and triglyceride levels. There were demonstrable improvements to NAFLD activity score (NAS) and fibrosis stage scoring after both surgeries. In RYGB, these beneficial changes to liver function resulted from the downregulation of pro-fibrotic and upregulation anti-fibrotic genes, as well as increased fatty acid oxidation and bile acid flux. For VSG, though similar alterations were observed, they were less potent. However, VSG did significantly downregulate pro-fibrotic genes and showed increased glycogen content paralleled by decreased glycogenolysis which may have contributed to the resolution of NAFLD. CONCLUSION/CONCLUSIONS:RYGB and VSG improve liver physiology and function, but RYGB is more efficacious. Resolutions of NAFLD in RYGB and VSG are achieved through different processes, independent of weight loss.
PMID: 35419698
ISSN: 1708-0428
CID: 5204402
RYGB Is More Effective than VSG at Protecting Mice from Prolonged High-Fat Diet Exposure: An Occasion to Roll Up Our Sleeves?
Stevenson, Matthew; Srivastava, Ankita; Lee, Jenny; Hall, Christopher; Palaia, Thomas; Lau, Raymond; Brathwaite, Collin; Ragolia, Louis
PURPOSE/OBJECTIVE:Understanding the effects of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on adipose tissue physiology is important for the treatment of obesity-related metabolic disorders. By using robust mouse models of bariatric surgery that closely resemble those performed in humans, we can compare the effects of RYGB and VSG on adipose physiology in the absence of post-operative confounds such as diet and lifestyle changes. MATERIALS AND METHODS/METHODS:RYGB and VSG were compared using a diet-induced mouse model of obesity. High-fat diet (HFD) was administered post-operatively and changes to white and brown adipose tissue were evaluated, along with alterations to weight, glucose homeostasis, dyslipidemia, and insulin sensitivity. RESULTS:After prolonged exposure to high-fat diet post-operatively, RYGB was effective in achieving sustained weight loss, while VSG unexpectedly accelerated weight gain rates. The resolution of obesity-related comorbidities such as glucose and insulin intolerance, dyslipidemia, and insulin sensitivity was improved after RYGB, but not for VSG. In RYGB, there were improvements to the function and health of white adipose tissue, enhanced brown adipose metabolism, and the browning of subcutaneous white adipose tissue, with no comparable changes seen for these factors after VSG. Some markers of systemic inflammation improved after both RYGB and VSG. CONCLUSION/CONCLUSIONS:There are significantly different effects between RYGB and VSG when HFD is administered post-operatively and robust mouse models of bariatric surgery are used. RYGB resulted in lasting physiological and metabolic changes but VSG showed little difference from that of its sham-operated, DIO counterpart.
PMID: 33856636
ISSN: 1708-0428
CID: 4889082
MTP In Adipocyte Regulates Basal Lipolysis By Inhibiting ATGL [Meeting Abstract]
Rajan, Sujith; Hussain, Mahmood; Lau, Raymond; Brathwaite, Collin; Villa-Cuesta, Eugenia
ISI:000727052100304
ISSN: 1930-7381
CID: 5479782
Surgical Mouse Models of Vertical Sleeve Gastrectomy and Roux-en Y Gastric Bypass: a Review
Stevenson, Matthew; Lee, Jenny; Lau, Raymond G; Brathwaite, Collin E M; Ragolia, Louis
Reviewed here are multiple mouse models of vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) that have emerged over the past decade. These models use diverse approaches to both operative and perioperative procedures. Scrutinizing the benefits and pitfalls of each surgical model and what to expect in terms of post-operative outcomes will enhance our assessment of studies using mouse models, as well as advance our understanding of their translational potential. Two mouse models of bariatric surgery, VSG-lembert and RYGB-small pouch, demonstrate low mortality and most closely recapitulate the human forms of surgery. The use of liquid diets can be minimized, and in mice, RYGB demonstrates more reliable and longer lasting effects on weight loss compared to that of VSG.
PMID: 31630327
ISSN: 1708-0428
CID: 4163622