Dietary tryptophan restriction selectively suppresses lipogenesis, lowers cholesterol, and reduces adiposity without altering food consumption
Abstract
We interrogated the consequences of removing individually each of the nine essential amino acids using defined diets in mice. Among the essential amino acids, only tryptophan (Trp) depletion induced rapid and selective fat loss with minimal effects on lean body mass while retaining normal feeding behavior. We named this intervention “Trypt-out.” Trypt-out prevented and reversed obesity, hepatic steatosis, and glucose intolerance in both leptin-deficient and diet-induced obesity. Trypt-out also remained highly effective even with obesogenic high-fat and high-sucrose diets. Mechanistically, short-term Trp depletion did not impair global protein synthesis but selectively resulted in profound inhibition of lipogenic and cholesterol biosynthetic enzymes. This resulted in reduction in cholesterol that exceeded the effects of statin therapy. Trp as a master regulator of systemic lipid homeostasis and establish Trypt-out as a well-tolerated, rapid- acting dietary strategy to selectively eliminate adiposity, normalize metabolic dysfunction, and lower cholesterol without reducing food consumption or lean mass.
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BibTeX
@misc{conaccisorrell2026dietary,
title = {{Dietary tryptophan restriction selectively suppresses lipogenesis, lowers cholesterol, and reduces adiposity without altering food consumption}},
author = {Maralice Conacci-Sorrell and pedro Augusto silva Nogueira and Lizbeth Perez-Castro and Niranjan Venkateswarran and Emily Parks and Kathleen Mannino and Yi-Heng Hao and Igor dos Santos and Ruth Gordillo and Jessica Kilgore and Isabella DePasquale and Joyane Eriom and Lei Dong and Lin Xu and Andrew Lemoff and Ralph DeBerardinis and Noelle Williams and Philipp Scherer},
howpublished = {Research Square},
year = {2026},
month = oct,
doi = {10.21203/rs.3.rs-10855823/v1},
url = {https://europepmc.org/article/PMC/PMC13742791},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dietary tryptophan restriction selectively suppresses lipogenesis, lowers cholesterol, and reduces adiposity without altering food consumption
AU - Maralice Conacci-Sorrell
AU - pedro Augusto silva Nogueira
AU - Lizbeth Perez-Castro
AU - Niranjan Venkateswarran
AU - Emily Parks
AU - Kathleen Mannino
AU - Yi-Heng Hao
AU - Igor dos Santos
AU - Ruth Gordillo
AU - Jessica Kilgore
AU - Isabella DePasquale
AU - Joyane Eriom
AU - Lei Dong
AU - Lin Xu
AU - Andrew Lemoff
AU - Ralph DeBerardinis
AU - Noelle Williams
AU - Philipp Scherer
PY - 2026
DA - 2026/10/12
PB - Research Square
DO - 10.21203/rs.3.rs-10855823/v1
UR - https://europepmc.org/article/PMC/PMC13742791
AB - We interrogated the consequences of removing individually each of the nine essential amino acids using defined diets in mice. Among the essential amino acids, only tryptophan (Trp) depletion induced rapid and selective fat loss with minimal effects on lean body mass while retaining normal feeding behavior. We named this intervention “Trypt-out.” Trypt-out prevented and reversed obesity, hepatic steatosis, and glucose intolerance in both leptin-deficient and diet-induced obesity. Trypt-out also remained highly effective even with obesogenic high-fat and high-sucrose diets. Mechanistically, short-term Trp depletion did not impair global protein synthesis but selectively resulted in profound inhibition of lipogenic and cholesterol biosynthetic enzymes. This resulted in reduction in cholesterol that exceeded the effects of statin therapy. Trp as a master regulator of systemic lipid homeostasis and establish Trypt-out as a well-tolerated, rapid- acting dietary strategy to selectively eliminate adiposity, normalize metabolic dysfunction, and lower cholesterol without reducing food consumption or lean mass.
SN - 2693-5015
ER -