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Daily transient coating of the intestine leads to weight loss and improved glucose tolerance. | LitMetric

Daily transient coating of the intestine leads to weight loss and improved glucose tolerance.

Metabolism

Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of General and GI Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Published: January 2022

AI Article Synopsis

  • Roux-en-Y gastric bypass (RYGB) surgery is considered the top treatment for obesity-related type-2 diabetes, but many patients hesitate to undergo it due to risks and permanent bodily changes.
  • A study tested an oral treatment called LuCI on rats, which was designed to replicate some benefits of RYGB without surgery, to see its effects on weight and blood sugar levels.
  • Results showed that rats given LuCI lost weight, had better glucose control, and absorbed fewer calories, indicating LuCI could be a viable alternative for managing weight and diabetes risk.

Article Abstract

Introduction: Roux-en-Y gastric bypass surgery (RYGB) has been shown to be the gold standard treatment for obesity associated type-2-diabetes (T2D), however many T2D patients do not qualify or are reluctant to proceed with surgery due to its potential risks and permanent changes to GI anatomy. We have previously described a novel oral formulation, LuCI, that provides a transient coating of the proximal bowel and mimics the effects of RYGB. Herein, we aim to investigate the outcome of chronic LuCI administration on weight and glucose homeostasis.

Methods: Sprague-Dawley rats on a high fat diet achieving diet-induced obesity (DIO) received 5 weeks of daily LuCI or normal saline as control (n = 8/group). Daily weights and glucose tolerance were monitored throughout the experiment. At 5 weeks, systemic blood was sampled through a surgically placed jugular vein catheter, before and during an intestinal glucose bolus, to investigate changes in key hormones involved in glucose metabolism. To elucidate the effects of LuCI on nutrient absorption, fecal output and food intake were measured simultaneously with the analysis of homogenized stool samples performed using bomb calorimetry.

Results: At 5 weeks, LuCI animals weighted 8.3% less and had lower fasting glucose levels than Controls (77.6 ± 3.8 mg/dl vs. 99.1 ± 2.7 mg/dl, P < 0.001). LuCI-treated animals had lower baseline insulin and HOMA-IR. Post-prandially, LuCI group had increased GLP-1 and GIP secretion following a glucose challenge. Serum lipid analysis revealed lowered LDL levels highlighting the potential to not only improve glucose control but also modify cardiovascular risk. We then investigated whether LuCI's effect on proximal bowel exclusion may play a role in energy balance. Bomb calorimetry analysis suggested that LuCI reduced calorie absorption with no difference in caloric consumption.

Conclusion: We demonstrated that LuCI recapitulates the physical and hormonal changes seen after RYGB and can ameliorate weight gain and improve insulin sensitivity in a DIO rat model. Since LuCI's effect is transient and without systemic absorption, LuCI has the potential to be a novel therapy for overweight or obese T2D patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666968PMC
http://dx.doi.org/10.1016/j.metabol.2021.154917DOI Listing

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