Blocking Gherlin May Be Key To Preventing Weight Gain After Dieting Interview with:

Dr. W. Stephen Brimijoin PhD Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Rochester, MN 55905

Dr. Brimijoin

Dr. W. Stephen Brimijoin PhD
Department of Molecular Pharmacology and Experimental Therapeutics
Mayo Clinic, Rochester, MN 55905 What is the background for this study? What are the main findings?

Response: The background for this study was:

1) Ordinary C57 black mice readily become obese when given unrestricted access to high-fat mouse chow.

2) If the obese mice are put on a forced calorie restricted diet they will regain their previous normal healthy weight.  However, if they are given unrestricted access to their previous “normal” low-fat mouse chow, they will rebound into obesity.  This effect can be seen as a model of human obesity and the difficulties that formerly obese men and women face in maintaining healthy body mass gained after dieting.

3) The literature on obesity provided reason to believe that this self-defeating behavioral cycle involves ghrelin, the so-called “hunger hormone.”

4) We had recently shown that the plasma enzyme called “butyrylcholinesterase” was a key regulator of active ghrelin. Therefore, it seemed plausible that raising enzyme levels would reduce ghrelin and, in turn, would blunt food craving.

To test this hypothesis, we used an AAV8 viral gene transfer agent encoding DNA for expression of the cholinesterase and another batch of viral vector encoding cDNA for the irrelevant protein, luciferase.  The main findings were closely in line with expectations.  On a high fat diet for several months, mice with active BChE vector gained weight to approximately the same degree as those with the control vector.  Both groups were then placed on a calorie-restricted diet of normal chow.  After several weeks, all mice had returned to their previous “healthy body weight.”

The next step was to give the two groups unrestricted access to normal chow.  The mice with the control vector ate far more than the mice given BChE vector, and they had far more ghrelin in their blood stream. Unsurprisingly, these animals rapidly began to accumulate fat.  In contrast, the mice with high BChE had low levels of circulating ghrelin, did not overeat, and remained within the range of healthy body weight. What should clinicians and patients take away from your report?

Response: General readers may be encouraged that novel interventions such as those in this pioneer study may serve as a powerful means of aiding weight control without being overwhelmed by cravings for food.  Scientists in the field of obesity may be interested in exploring the safety and efficacy of multiple modes of gene therapy directed towards ameliorating obesity worldwide. What recommendations do you have for future research as a result of this study?

Response: To test this hypothesis it seems desirable to carry out similar studies with animals of a different species, possibly including primates.  If the results are similar, as seems likely given ghrelin’s near universal role in vertebrates, and if the enzyme gene transfer proves to be fundamentally benign, as we expect, there would be a green light for potential human trials. 

Disclosures: Mayo Clinic has filed a patent application based on the use of BChE gene transfer to regulate eating behavior Thank you for your contribution to the community.


Vicky Ping Chen, Yang Gao, Liyi Geng, and Stephen Brimijoin

Butyrylcholinesterase gene transfer in obese mice prevents postdieting body weight rebound by suppressing ghrelin signaling PNAS 2017 ; published ahead of print September 25, 2017, doi:10.1073/pnas.1706517114

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.


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Last Updated on September 27, 2017 by Marie Benz MD FAAD