Why Eating Just One Potato Chip Is So Hard

Author: Osaka Metropolitan University
Published: 23 Dec 2022 - Updated: 23 Aug 2026
Publication Details: Peer-Reviewed | Research, Study, Analysis

Table of Contents:
Synopsis - Definition - Overview - FAQs - Insights, Updates - Related Content

Synopsis

This research, a peer reviewed study from Osaka Metropolitan University published in the FASEB Journal, identifies a specific brain circuit that helps put the brakes on overeating. Scientists already knew that the CREB-regulated transcription coactivator 1 (CRTC1) gene is linked to human obesity, but because the gene is active in every neuron in the brain, no one could say which cells actually carried out the appetite-suppressing job. A team led by Associate Professor Shigenobu Matsumura narrowed the search to neurons that express the melanocortin-4 receptor (MC4R), then bred mice that produced CRTC1 everywhere except in those cells. On ordinary chow the animals looked normal, but once fed a high-fat diet they ate more, gained significantly more weight than controls, and developed insulin resistance and diabetes. The finding matters to anyone who struggles with weight gain, appetite control, or type 2 diabetes, and it is particularly relevant to older adults and people with disabilities, for whom reduced mobility, medication side effects, and limited food choices can make weight management far harder. By pinpointing where in the brain fat and sugar cravings are regulated, the work gives researchers a concrete molecular target rather than a vague appeal to willpower.*

At a Glance

1 - Mutations in the MC4R gene are a known cause of human obesity. That link is what led the team to test whether CRTC1 acts through those same neurons.
2 - On a standard diet, mice lacking CRTC1 in MC4R neurons weighed the same as control mice. The difference only emerged once a high-fat diet was introduced.
3 - The work was carried out at the Graduate School of Human Life and Ecology and reported on November 9, 2022. Matsumura has said the goal is a better understanding of what drives people to overeat.
4 - CRTC1 was previously known as TORC1, short for Transducer Of Regulated CREB activity 1. It is expressed in a limited set of tissues, including fetal brain and liver, adult heart, skeletal muscle, liver, salivary glands, and parts of the central nervous system.

Topic Definition

CRTC1 Gene: The CRTC1 gene encodes CREB-regulated transcription coactivator 1, a protein once called TORC1, or Transducer Of Regulated CREB activity 1. Rather than acting on its own, it works as a partner molecule that helps switch other genes on and off inside cells, and it turns up in a fairly narrow set of tissues: the fetal brain and liver, the adult heart, skeletal muscle, liver, and salivary glands, and scattered regions of the adult central nervous system. In the brain its best documented job is metabolic. When CRTC1 is missing from neurons carrying the melanocortin-4 receptor, animals eat past the point of fullness on fatty food, put on weight, and lose the ability to handle blood sugar properly, which is why researchers now treat the gene as one of the molecular controls linking appetite, high-calorie diets, obesity, and insulin resistance in humans.

Overview

CRTC1 deficiency, specifically in melanocortin-4 receptor-expressing cells, induces hyperphagia, obesity, and insulin resistance.

A potato chip (North American English; often just chip) or crisp (British and Irish English) is a thin slice of potato that has been either deep fried, baked, or air fried until crunchy.

High-calorie foods - high in fat, oil, and sugar - can taste good but often cause overeating, leading to obesity and major health problems. But what stimulates the brain to cause overeating?

Recently, it has become clear that a gene called CREB-Regulated Transcription Coactivator 1 (CRTC1) is associated with obesity in humans. When CRTC1 is deleted in mice, they become obese, indicating that functioning CRTC1 suppresses obesity. However, since CRTC1 is expressed in all neurons in the brain, the specific neurons responsible for suppressing obesity and the mechanism present in those neurons remained unknown.

To elucidate the mechanism by which CRTC1 suppresses obesity, a research group led by Associate Professor Shigenobu Matsumura from the Graduate School of Human Life and Ecology at Osaka Metropolitan University focused on neurons expressing the melanocortin-4 receptor (MC4R).

Osaka Metropolitan University scientists have revealed that the transcription cofactor gene CRTC1 mediates the obesity-suppressing effects of melanocortin-4 receptor (MC4R) by regulating appetite for fats and oils, high-fat diet metabolism, and blood sugar - Image Credit: Shigenobu Matsumura, Osaka Metropolitan University.

They hypothesized that CRTC1 expression in MC4R-expressing neurons suppressed obesity because mutations in the MC4R gene are known to cause obesity. Consequently, they created a strain of mice that expresses CRTC1 normally except in MC4R-expressing neurons where it is blocked to examine the effect that losing CRTC1 in those neurons had on obesity and diabetes.

When fed a standard diet, the mice without CRTC1 in MC4R-expressing neurons showed no changes in body weight compared to control mice. However, when the CRTC1-deficient mice were raised on a high-fat diet, they overate, became significantly more obese than the control mice, and developed diabetes.

"This study has revealed the role that the CRTC1 gene plays in the brain and part of the mechanism that stops us from overeating high-calorie, fatty, and sugary foods," said Professor Matsumura. "We hope this will lead to a better understanding of what causes people to overeat."

The research results were published in the FASEB Journal on November 9, 2022.

Frequently Asked Questions

NOTE: Researched FAQs by Disabled World (DW)

Is CRTC1 the only gene linked to obesity in humans

No, obesity involves many genes, including FTO, MC4R, LEP and POMC, along with diet, sleep, stress, activity levels and medication effects. CRTC1 is one contributing factor rather than a single cause.

Can a person be tested for CRTC1 variants

Some research and clinical genetics laboratories can sequence CRTC1, but routine testing is not offered as part of standard obesity care because no treatment currently depends on the result.

Does this study mean willpower has nothing to do with overeating

Not quite. Biology sets how strong an appetite signal feels, while environment and habits shape how often that signal is triggered, so behavior and genetics both play a part.

What is the melanocortin-4 receptor

MC4R is a receptor found on certain brain neurons that helps regulate food intake and energy balance. Inherited faults in the MC4R gene are among the most common single gene causes of severe obesity.

Do results in mice usually apply to people

Mouse studies identify mechanisms and targets, but human trials are required to confirm them. Appetite pathways are broadly similar across mammals, which is why this line of work is considered promising.

Why do fatty and sugary foods drive overeating more than other foods

They deliver a large number of calories in a small volume and strongly activate reward circuits in the brain, so fullness signals arrive later than the urge to keep eating.

Could a drug based on CRTC1 be developed

It is possible in principle, but the gene influences many processes beyond appetite, so any therapy would need to act narrowly to avoid unwanted effects. No such drug exists at present.

What practical steps help people who find high-calorie snacks hard to stop eating

Portioning snacks into small containers, keeping them out of direct sight, eating enough protein and fiber at meals, and getting adequate sleep all reduce the frequency and intensity of cravings.

Insights, Analysis, and Developments

Editorial Note: The reason one potato chip so rarely stays one chip has less to do with character than with chemistry. What this study adds is a location: the appetite brake sits in melanocortin-4 receptor neurons, and CRTC1 is the switch that keeps it working. Take that switch away and the animals behave normally until fat enters the picture, at which point intake climbs, weight follows, and blood sugar control falls apart. That sequence is worth noting, because it suggests the gene is not a general hunger regulator but something closer to a fat-and-oil specific governor. For clinicians, dietitians, and caregivers who work with people facing obesity, metabolic syndrome, or diabetes, the practical takeaway is that food environment and genetics interact rather than compete, and that advice to simply eat less misses the mechanism entirely. Whether this pathway can be safely targeted with drugs remains an open question, and mouse metabolism is not human metabolism, but the study narrows a very large problem down to a very specific set of cells - which is usually how useful treatments begin.*

Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Osaka Metropolitan University and published on 23 Dec 2022, this content may have been edited for style, clarity, or brevity.

* Editorial additions by Ian C. Langtree.