Reprogramming of defended body weight after Roux‐En‐Y gastric bypass surgery in diet‐induced obese mice

Abstract

Objective Roux-en-Y gastric bypass surgery (RYGB) results in sustained lowering of body weight in most patients, but the mechanisms involved are poorly understood. The aim of this study was to obtain support for the notion that reprogramming of defended body weight, rather than passive restriction of energy intake, is a fundamental mechanism of RYGB. Methods Male C57BL6J mice reaching different degrees of obesity on a high-fat diet either with ad libitum access or with caloric restriction (weight-reduced) were subjected to RYGB. Results RYGB-induced weight loss and fat mass loss was proportional to pre-surgical levels, with moderately obese mice losing less body weight and fat compared with very obese mice. Remarkably, mice that were weight-reduced to the level of chow controls before surgery, immediately gained weight after surgery, exclusively accounted for by lean mass gain. Conclusions The results provide additional evidence for re-programming of a new defended body weight as an important principle by which RYGB lastingly suppresses body weight. RYGB appears to selectively abolish defense of a higher fat mass level, while remaining sensitive to the defense of lean mass. The molecular and physiological mechanisms underlying this re-programming remain to be elucidated.

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

“…In accordance with previous human (Kenler et al, 1990; Olbers et al, 2006; Thomas and Marcus, 2008) and rodent (Zheng et al, 2009; le Roux et al, 2011; Shin et al, 2011b; Hao et al, 2016) studies, we demonstrated that RYGB reduces HF intake and preference using an established rat model (Hankir et al, 2015; Seyfried et al, 2016). We found that this was associated with widespread reductions in brain MOR availability, particularly in the striatum.…”

“…This forms an important basis for gaining a better understanding of the central molecular underpinnings of successful long-term weight reduction unique to bariatric surgery. Additionally, it remains unclear whether alterations in brain MOR signaling following Roux-en-Y gastric bypass (RYGB), the most frequently employed bariatric surgical procedure, relates to the documented postoperative suppression in fat appetite in human (Kenler et al, 1990; Olbers et al, 2006; Thomas and Marcus, 2008) and animal (Zheng et al, 2009; le Roux et al, 2011; Shin et al, 2011b; Hao et al, 2016) studies. We therefore performed detailed fat intake and preference measurements in conjunction with in vivo small-animal [ 11 C]carfentanil PET imaging studies in lean and diet-induced obese rats in comparison with animals that experienced identical weight loss from RYGB or chronic caloric-restriction.…”

Persistent metabolic adaptation 6 years after “The Biggest Loser” competition

“…After returning home from the NIH Clinical Center, subjects drank from a stock solution of 10% 18 O enriched H 2 O and 99% enriched 2 H 2 O at a dose of 1.5 g/kg body weight followed by 100 to 200 mL tap water to rinse the dose container. Spot urine samples were collected at 1.5, 3, 4.5, and 6 h after administration and once daily over the next 13 days when the subjects were instructed not to change their usual routine.…”

Can Vestibular Stimulation be Used to Treat Obesity?

“…Possible ways to do so include eating a diet rich in polyunsaturated fatty acids, or reducing long‐term dietary intake of sugar and saturated fats, both of which are thought to facilitate the recovery of hypothalamic neurons . Remarkably, it is also now believed that bariatric surgery actually works, at least in part, by lowering the set‐point, rather than by simply decreasing caloric intake . This is because people who undergo such operations do not continue to get thinner and thinner but rather reduce to a new body weight about which they then settle.…”