Nima Saeidi, an assistant professor of surgery at Harvard Medical School and Massachusetts General Hospital and a member of the Center for Engineering in Medicine, had started down one career path when a lecture on Roux-en-Y gastric bypass surgery redirected him.The MGH lecture outlined not just the procedure’s striking effectiveness for weight loss — averaging 40 percent — but also its promise against diabetes, high blood pressure, cholesterol, and fatty-food cravings. Saeidi, an assistant in bioengineering at MGH, halted his work in tissue engineering and began to study gastric bypass.“To me, it’s really a mystery,” said Saeidi, “and it seems to be like a miracle.”The idea of a compound that mimics the positives of Roux-en-Y is particularly enticing amid twin national epidemics of obesity and diabetes. A therapy that conferred the surgery’s benefits while avoiding its less healthy side effects — brittle bones, vitamin deficiency, anemia, and increased rates of alcoholism — would likely add significantly to the 45,000 morbidly obese patients the procedure helps annually.The problem is scientists still don’t know how it works.In Roux-en-Y, physicians make a small pouch out of the upper portion of the stomach and then cut and reattach the small intestine to the pouch, bypassing the entire lower stomach and the first few feet of the small intestine. This transformation of the stomach into a pouch makes patients feel full quickly, while food’s rapid passage into the intestine alters digestion and absorption of calories — as well as of minerals and vitamins, the cause of some of the surgery’s negative side effects.The surgery was developed decades ago as a treatment for stomach ulcers, and was first used as a correction for morbid obesity by University of Iowa physicians in 1967. Follow-up research uncovered dramatic benefits independent of weight loss.For example, though Type 2 diabetes risk is tied to obesity, post-Roux-en-Y resolution of the disease — more than 80 percent of patients are cured — is not solely a weight-loss phenomenon.“We see effects happening within two to three days,” Saeidi said. “Patients get surgery and they’re completely diabetic, they need insulin or metformin medication. And many of them leave the hospital without any medication. It is just puzzling how this is happening and what is causing it.”There were 64 Roux-en-Y procedures at MGH last year. The surgery has been shown to affect insulin sensitivity and production of the hunger hormones ghrelin and leptin. It also alters the composition of a patient’s microbiome, the intestinal bacteria that scientists are beginning to understand play a major role in health. Harvard researchers are targeting obesity and its cousin, diabetes Alcohol abuse after weight loss surgery? Study suggests possible alternative to gastric bypass surgery Researchers gather at Radcliffe to investigate gut-brain communication Related Obesity? Diabetes? We’ve been set up Major weight loss tied to microbes Initially, Saeidi said, researchers searched for a single enzyme or hormone responsible for the changes. But consensus has gradually turned away from a “silver bullet” for what appears to be a fundamental shift in metabolism.“The previous work was on single tissue, but it became very apparent it’s not just a story about one single organ or one single tissue,” Saeidi said. “It is the crosstalk and interaction between different organs that really drives the systemic effects.”That crosstalk is likely to involve a network of cascading changes in fat, muscle, the liver, and intestines. To better probe that complexity, Saeidi and colleagues have turned to new rodent models, spectroscopic instruments, and novel informatics techniques that shift inquiry from a traditional hypothesis-based, step-by-step exploration to one that seeks to reverse-engineer the problem, by searching broadly for postoperative chemical changes in the body and then working to understand them.“This is an agnostic, hypothesis-generation tool,” said Gautham Sridharan, a recent fellow in Saeidi’s lab and first author of a paper on their work published in the journal Technology. “Post RYGB, we see all these changes … in metabolism. It gives us some clue that maybe we should further investigate that pathway.”In a Roux-en-Y rodent model, Saeidi’s team identified more than 1,300 liver proteins and searched for changes in their concentration 30 days later. Eighty-two had changed and two of them, Thrsp and Acot13, appeared to be potential drug targets. Though that may seem a promising start, Sridharan noted that the study examined only one organ and at just one point in what appears to be a dynamic post-surgery process involving several organs.Future research, Saeidi said, will examine compounds whose altered concentrations in one organ move through the blood to where they can affect others.“Ideally, we want to have a sense of the dynamics of the changes that occur in different organs and how different organs interact with each other,” Saeidi said.
View comments Ginebra beats Meralco again to capture PBA Governors’ Cup title Don’t miss out on the latest news and information. Japeth Aguilar embraces role, gets rewarded with Finals MVP plum Blake Griffin led Detroit with 20 points, while Andre Drummond added 13.Detroit came into the game having won six straight at home, including the first five games on its current homestand, but fell six points short of its previous season low.FEATURED STORIESSPORTSGinebra beats Meralco again to capture PBA Governors’ Cup titleSPORTSJapeth Aguilar wins 1st PBA Finals MVP award for GinebraSPORTSGolden State Warriors sign Lee to multiyear contract, bring back ChrissThe Thunder led 50-40 at halftime behind 14 points from Adams and 10 from Jeremi Grant. Griffin had 15 points for Detroit, which shot 34.7 percent from the floor.Detroit’s offense continued to struggle in the second half without Reggie Bullock, who left the game in the first quarter with an ankle injury. The Thunder took a 71-51 lead midway through the third quarter and led by 28 at the end of the period. In the fourth, Oklahoma City led by as many as 35. Oklahoma City Thunder forward Abdel Nader (11) runs into Detroit Pistons guard Bruce Brown (6) during the second half of an NBA basketball game, Monday, Dec. 3, 2018, in Detroit. (AP Photo/Carlos Osorio)DETROIT— Steven Adams scored 21 points, Russell Westbrook added 18 and the Oklahoma City Thunder ended the Detroit Pistons’ five-game winning streak with a 110-83 victory Monday night.Paul George added 17 points for the Thunder, who are 15-3 since losing their first four games.ADVERTISEMENT Gretchen Barretto’s daughter Dominique graduates magna cum laude from California college ‘Mia’: Rom-com with a cause a career-boosting showcase for Coleen Garcia Lights inside SMX hall flicker as Duterte rants vs Ayala, Pangilinan anew MOST READ After winning title, time for LA Tenorio to give back to Batangas folk Nadine Lustre’s phone stolen in Brazil LATEST STORIES Big 3 Durant, Curry, Thompson lead Warriors to 128-111 win over Atlanta Carpio hits red carpet treatment for China Coast Guard PLAY LIST 02:14Carpio hits red carpet treatment for China Coast Guard02:56NCRPO pledges to donate P3.5 million to victims of Taal eruption00:56Heavy rain brings some relief in Australia02:37Calm moments allow Taal folks some respite03:23Negosyo sa Tagaytay City, bagsak sa pag-aalboroto ng Bulkang Taal01:13Christian Standhardinger wins PBA Best Player award No.13 lucky for Orlando Bloom Thunder: At the Brooklyn Nets on Wednesday night.Pistons: At the Milwaukee Bucks on Wednesday night.Sports Related Videospowered by AdSparcRead Next Lights inside SMX hall flicker as Duterte rants vs Ayala, Pangilinan anew Adams made his first seven field-goal attempts, along with five free throws, and forced Drummond and Zaza Pachulia to the bench with four fouls each. The Pistons finished the third quarter with Griffin at center and 6-foot-7 Stanley Johnson at power forward.TIP-INSThunder: Oklahoma City is 15-5 against the Pistons since leaving Seattle. … The Thunder, who came into the game with the league’s best defensive rating, are now 4-0 when holding their opponents under 90 points.Pistons: Detroit fell short of its first seven-game home winning streak since March 14-April 4, 2008. … Drummond went 1-for-2 from the free-throw line and has now missed 19 of his last 24 attempts.UP NEXTADVERTISEMENT