The Rats Who Starved to Death While Obese

Lessons from truly barbaric experiments…

This week’s post is insane for many reasons. Buckle up.

First, let’s set the wayback machine to 1961. An era much like today—a dispute with Russia pushing the world to the brink of WW3, a prominent Kennedy at war with the CIA, chaos in the Middle East, etc.

But one thing was different back then: attitudes toward animal cruelty.

Apparently, it was cool to torture rats, if done in the hallowed name of Science.

Enter Lois and Theodore Zucker, researchers fascinated by a strain of lab rat with a deeply strange metabolism. At birth, these rats looked normal. But as they nursed, they accumulated fat at a breathtaking rate. Within weeks, they were nearly twice the size of their lean littermates, their blood turning cloudy from excess lipids leaking into circulation.

What the hell was happening to these creatures?

And what did it all mean?

The Rats Who Defied Dieting

Like most people today, the Zuckers assumed obesity was a simple case of eating too much. And at first glance, the Zucker rats fit the mold perfectly—they were voracious eaters, outpacing their lean littermates in food intake. Their obesity, it seemed, was a textbook case of calories in, calories out (CICO): they ate too much, so they got fat. Case closed.

But then the researchers did something clever. They restricted the Zucker rats’ diets, feeding them the exact same portions as their lean counterparts. By all logic, the rats should have slimmed down. They did not. Their fat depots refused to shrink.

Intrigued—and possibly in a supervillain-y mood—the researchers dialed up the metabolic torture.

The rats’ food bowls were nearly emptied, leaving them just enough kibble to stave off death. In any normal animal, this level of caloric deprivation generally forces the body to burn its fat stores for survival. That’s (part of) what fat is for—to keep you alive when food is scarce.

But even starvation wasn’t sufficient to unlock the Zuckers’ vast reserves of adipose tissue. Instead, their bodies chose to devour muscle and organs for fuel. Finally, in a grotesque finale, they literally ate their own hearts and died of heart failure.

Yet even in death, their bodies still carried significant excess fat—more than healthy lean rats.

This was certainly a tragedy for the Zuckers and their next of kin. But it was also deeply perplexing because it violated everything we think we know about fat loss.

What Happened Inside Those Rats?

A 2024 paper in Obesity Reviews by Friedman et al. takes a deep dive into the biology. The authors note:

“The early, pre-weaning increase in adiposity in fa/fa [Zucker] rat pups is associated with increased adipose tissue lipoprotein lipase (LPL) activity, lipogenesis, lipogenic enzyme activity, and expression of glucose transporter 4 expression, all of which would favor substrate shunting toward storage.”

Translation? It wasn’t about overeating. The Zucker rats shuttled fuel into deep storage and then refused to release it, no matter how dire the circumstances became.

Other Animals That Broke CICO

For nearly a century, metabolic experiments on lab animals have repeatedly demonstrated phenomena like this, which strongly imply that fat storage and fat burning are regulated independently of food intake.

And yet, the human obesity research community has largely ignored these findings.

The prevailing narrative—that obesity is simply a failure of willpower and thus psychological in nature—has dominated, leaving physiological explanations on the sidelines. That the only organ these researchers seem to care about is the brain suggests they may have forgotten how to use theirs.

Friedman et al. highlight other curiosities, such as:

The ob/ob Mouse - Storing Fat While Eating Less

The ob/ob mouse carries a mutation that disrupts leptin signaling, a key hormonal regulator of body fat. These mice gain fat at an alarming rate—and it was long assumed this was simply due to overeating. But when researchers cut their food intake by 25%, forcing them to eat significantly less than normal mice, they still deposited three times as much body fat (!!) over seven months.

Less food. More fat.

The Yellow Mouse: More Fat Per Calorie Consumed

First documented in 1927, the yellow mouse gains more body fat per calorie consumed than normal mice. Even when eating 18% fewer calories, these mice maintain the same body weight—but with a significantly higher proportion of that weight stored as fat.

The VMH-Lesioned Rat

This one is particularly brutal. In another example of scientific barbarism, researchers in the mid-20th century began lesioning the ventromedial hypothalamus (VMH)—a brain region involved in energy regulation—in lab rats.

What happened next was astonishing.

Even when post-surgery food intake was strictly controlled—meaning these rats were prevented from overeating—they still became obese. Within just one hour of hypothalamic damage, their bodies shifted fuel partitioning toward fat storage, ramping up lipogenesis (fat creation) and fatty acid esterification (locking fat away in storage) while simultaneously decreasing lipolysis (fat burning).

One hour!

No change in food intake. Just a switch flipped, and these rats suddenly began storing fat like crazy.

The Willpower Delusion

Again, I cannot stress this enough: these experiments have been effectively ignored by the human obesity research community.

If you asked, say, Marion Nestle—perhaps the most famous exponent of the calories-in, calories-out (CICO) idea (one of her books is literally titled Why Calories Count)—I’d bet good money she has devoted nary a nanosecond to contemplating these rat torture experiments.

And if she—or any other CICO true believer—were forced to engage with this data, their explanations would be intensely unsatisfying.

I know this because I’ve seen it happen.

About ten years ago, when I was much more involved in online debates about CICO, I got into a lengthy email exchange with a well-known doctor—a respected advocate of scientific skepticism and evidence-based medicine.

I laid out arguments much like the ones I’ve presented here. I asked, how can the CICO framework explain the Zucker rats? How can it account for fat accumulation in animals that aren’t overeating?

She wrote back—and I quote:

“I am not skeptical of calories-in, calories-out because I’ve seen it work for my dog.”

That was her response.

Not a word about the Zucker rats. Not a single attempt to address the data. Just “I put my dog on a diet, and he lost weight.” Yeesh.

I’ve also encountered another CICO favorite: the grotesque observation that there were no obese survivors of the concentration camps in World War II.

The argument, while blunt, is obvious enough: if you induce a calorie deficit large enough, fat loss must happen.

Fair enough. Leaving aside the macabre implications—and the fact that my great-great-grandfather died in one of those camps—I get what they’re trying to say.

But even this tragic historical example misses a key point. Yes, extreme starvation eventually burns fat. But the body doesn’t simply “spend” fat whenever calories run low—it follows a regulated sequence for energy use. And often, that “something” it burns isn’t stubborn excess fat—but muscle, organs, and essential tissues.

This is why starvation victims don’t just look thin—they look emaciated. Their bodies are disintegrating.

The Zucker rats were proof of this in its most extreme form. Even at the point of death, their bodies still clung to fat while devouring muscle and organs. The body can be forced into a calorie deficit, but that doesn’t mean it will burn fat efficiently.

Because fat storage isn’t about math. It’s about biology.

Using the Farmer Model to Bring Sense and Humanity to the Discussion

These grueling animal experiments force us to rethink obesity itself. It’s not simply a matter of eating too much. It’s a dysfunction of energy regulation, in which the body hoards fat and refuses to let it go.

The Farmer Model makes this easy to grasp.

Fat isn’t sitting in a vault, waiting to be withdrawn like money in a bank account—it’s part of a living energy system, more like water in an ecosystem.

We can visualize body fat as reservoirs, canals, streams, and underground aquifers. What determines whether fat is burned isn’t just how much food is coming in (rainfall), but how the land itself is shaped—its topography.

Now let’s go back to the Zucker rats.

Imagine a plot of farmland where, due to genetics, the land is warped—full of deep basins where water naturally pools. In normal conditions—when food intake is moderate—the land just holds more water than usual. The crops still grow, but the terrain is always wetter, always marshy.

Now, imagine a drought. The rainfall stops. The crops begin to wither. The soil dries out and cracks. But the water is still there. It’s locked in deep reservoirs and underground aquifers, trapped where it can’t be accessed. The crops die of thirst—while just a few feet away, massive pools of water remain untouched.

This ==> the Zucker rats.

It’s also the ob/ob mouse, who gains fat even when eating significantly less food than normal mice. It’s the yellow mouse, who stores more fat per calorie consumed. In every case, the metabolic landscape is skewed, sending energy into storage rather than circulating it freely.

And then there are the VMH-lesioned rats, the most haunting. Remember: researchers damaged the ventromedial hypothalamus (VMH)—a key brain region involved in metabolism. And within ONE HOUR, their bodies flipped into fat-storage overdrive. No change in food intake. No gradual weight gain. Just a switch flipped.

It was as if the instrument that damaged their brain also gouged out a massive hole in their metabolic farm. A giant pit appeared in the land—immediately, water rushed into it. From that moment on, their metabolic landscape had permanently changed. Even if food was restricted afterward, it didn’t matter—the land had been reshaped. Water now drained straight into storage before it could nourish the crops.

Obesity Isn’t an Overeating Disorder—It’s a Fuel-Partitioning Disorder

This is what the Farmer Model so clearly helps us visualize.

• It’s not about whether food is too delicious.

• It’s not about whether you’re hitting 10,000 steps a day.

• It’s not even about whether you’re “tracking your macros.” (And I say this as a devoted defender of the carbs-insulin hypothesis)

The core questions should be along the lines of:

• Why does the body partition fat the way it does?

• Is that partitioning normal?

• If not, what can be done about it?

These are the questions that actually matter.

And once we start asking these questions, perhaps we can stop blaming people for biology—and start figuring out how to fix it. Maybe then—just maybe—the torture of our mammalian cousins won’t have been entirely in vain.