The Hunger Games of The Second Brain

If you’ve sensed “butterflies” in your stomach before a stage performance, felt your “stomach churn” upon hearing a horrifying story, or simply made a decision based on your “gut feeling,” then you’ve experienced your second brain at work. Turns out, these commonly used phrases unravel a piece of hidden truth – the brain also functions in your gut.
The nervous system that lines your gut, the enteric nervous system (ENS), is popularly called the “second brain.” This complex network of over 100 million neurons along the gastrointestinal tract works independently of any commands from the brain! It’s as if the brain needed to outsource some of its functions and started an on-site system of neurons along the digestive tract. The ENS manages the body’s digestive system using the same functional machinery as the brain – a network of neurons, neurotransmitters and proteins.


The ENS plays an important role in governing food habits via bidirectional communication with the central nervous system (CNS). The sight of freshly baked pizza stimulates your appetite when it’s mealtime! Conversely, when we are stuffed after a huge, sumptuous meal, even the mention of food seems nauseating. These feelings are proof of communication between the ENS and CNS. A top-down communication occurs when hunger is triggered upon an external stimulus (the sight of pizza), and a bottom-up communication is responsible for the, “I can’t possibly eat anymore” state of mind!

In the 1940s, classic lesion experiments in rats gave rise to a dual center hypothesis for food intake – one center promotes eating and the other stops eating behavior. Rats with bilateral lesions in the lateral hypothalamus stopped eating and showed anorexic behaviors, indicating that this region was the hunger center of the brain. Lesions in the ventromedial hypothalamus elicited a voracious appetite leading to over-eating and an obese phenotype, so this region was labeled the satiety center.


While these experiments revealed important information about the hypothalamic nuclei involved in food intake, more recent versions of the experiment showed that the anorexic rat would not starve until death, but would resume normal eating habits upon reaching a certain low body weight. The same holds true for the obese rat, which would stop over-eating after a certain set point of high body weight. These observations show that feeding behavior are not only governed by inputs from neuronal signals (which were cut off by the lesion), but also by some food-related blood-borne feedback signals, like insulin and glucose, which are known as humoral signals.

So, what humoral signal makes us hungry? The hormone responsible for arousing hunger in our body is ghrelin. Before meals, ghrelin is released in the stomach, where it stimulates hunger. It binds to receptors in the hypothalamus causing the release of orexigenic (appetite-inducing) neuropeptides to enhance food intake.

What makes us stop eating? The protein hormone responsible for making us feel satiated is leptin. After meals, leptin is released from adipocytes (fat cells) and sends signals to the hypothalamus that the body has enough energy reserves, so we stop eating! It counteracts the effects of orexigenic neuropeptides and promotes synthesis of other appetite suppressants.

If these two hormones act in conjunction, then why do we overeat? It turns out, high levels of leptin (the food STOP signal) make the brain’s satiety center insensitive to it, causing us to eat even though the body is trying to hold us back from it!


The enteric nervous system, although seemingly hidden, is one of the most significant factors in controlling our body weight. Amidst the fanfare of the central nervous system, we forget the quiet actions of the neurons in our gut. But when these neurons need our attention before a meal, they are sure to let you know with a growl!



Mayer E.A. (2011). Gut feelings: the emerging biology of gut–brain communication, Nature Reviews Neuroscience, 12 (8) 453-466. DOI: 

Images adapted from Corbis/Food Passionates,,, and by Anita Ramanathan



Anita met neuroscience during her undergraduate project, and it was love at first sight. While majoring in biotechnology at the B.M.S. College of Engineering, Bangalore, she had the opportunity to learn about biochemical subtyping as a method for biomarker discovery in neurodevelopmental disorders. She then pursued a Master’s in Biochemistry and Molecular Biology at USC. During her thesis project, her interest in translational neuroscience further evolved as she studied a kinase pathway (PI3K) highly implicated in autism. She currently belongs to the Neuroscience Graduate Program at USC and works on components of the blood-brain barrier and its integrity in animal models of neurological disorders. Outside the lab, Anita is very enthusiastic about educational and scientific storytelling! Some of her parallel interests include consumer psychology and behavior.

One thought on “The Hunger Games of The Second Brain

  • January 6, 2014 at 6:08 pm

    Attractive section of content. I just stumbled upon your web site and in accession capital to
    assert that I get in fact enjoyed account your blog posts.
    Anyway I’ll be subscribing to your feeds and even I achievement
    you access consistently fast.

Comments are closed.