This was initially meant to be a post on fatty liver disease, but it led me into a rabbit hole on ectopic fat that even I, as a preventative medicine physician, was naive to. Opening my eyes to an area that we will realize to play a heavy role in chronic disease. Especially as AI and the collapsing cost of diagnostics such as full-body MRIs converge.
It also led me to build a deeper research layer for Zinda which we have been busy with for the past month. More on this later this week!
The Thrifty Engine left us with an unanswered question. If South Asian mitochondria are tightly coupled and our brown fat is sparse, surplus calories have no thermogenic exit. They can’t be burned off as heat, and at our typical activity levels they often can’t be burned off as ATP either. So where do they go?
The answer is the next layer of the framework: the Overflow Tank.
It’s where the surplus lands when the body’s safe storage shed, subcutaneous fat, has hit its ceiling and the dispersal routes are partly closed. The calories end up in the liver, the pancreas, the muscle, the heart, the kidneys, and the walls of the blood vessels. None of those organs are designed for that job.
This piece is the depot tour. It’s also, in my view, the framework’s most clinically important under-discussed concept; partly because the depots that matter most have the least research behind them. As full-body MRI, opportunistic CT, DEXA-derived body composition, and AI-assisted imaging become more common, medicine is going to start seeing what BMI has been hiding. South Asians may be the first population where that imaging shift rewrites the clinical story.
It’s a long piece so TL;DR
South Asians don’t necessarily carry more fat than Europeans. We carry it in the wrong places, inside the liver, the pancreas, threaded through the muscle, wrapped around the heart, pressed into the kidneys
Visceral fat and ectopic fat are not the same thing. Visceral fat is belly-cavity fat around organs. Ectopic fat is fat inside or directly on organs that are not supposed to store it; liver, pancreas, muscle, heart, kidney, blood vessels. Visceral fat is the warning light; ectopic fat is often where the organ damage happens
The mechanism is “forced spillover”: our mitochondria are tightly tuned for efficiency and our brown fat is reduced, so we have no thermogenic route to dump surplus calories. At the same time, our subcutaneous fat hits its storage ceiling at lower BMI than Europeans. Surplus has nowhere to go but somewhere it doesn’t belong
The medical literature obsesses over hepatic fat (NAFLD), 26 of 31 ethnic-comparison studies focus on liver fat, and largely ignores pancreatic, epicardial, intramuscular, renal sinus, and perivascular fat. The under-studied depots may matter most
The pancreatic fat story is the one I’d most want patients and physicians paying attention to. Fat infiltrating the pancreas directly poisons beta cells. This is plausibly why so many lean South Asians develop diabetes at young ages despite “normal” weight
The intervention story is not “lose weight.” It is expand safe storage capacity, shrink the surplus at source, and reopen the dispersal route. That changes how we think about exercise, food timing, and which medications are right for which patients
Picturing the Spillover
Imagine your body as a household with one shed in the backyard for storing surplus supplies. The shed is your subcutaneous fat, the soft fat under your skin. It is, when working properly, the safest place to keep extra calories. It’s quiet. It doesn’t bother anyone, it has valuable function in storing heat and energy. It releases supplies slowly when needed.
For most Europeans, the shed is large. It expands when more supplies arrive. New shelves get built. New rooms get added. The household stores its surplus calmly, even at higher caloric loads.
For most South Asians, the shed is smaller. And, this is the key, when the shed gets full, we don’t easily build new rooms. Our adipocytes (fat cells) tend to enlarge rather than multiply as we previously discussed. That works for a while. But there’s a ceiling.
When the shed fills up and can’t expand, the surplus has to go somewhere. So we start storing supplies in the kitchen. Then In the laundry room. Then the bedroom. Inside the engine (or frunk) of the car. Eventually, even the safe where the family heirlooms are kept.
That’s the Overflow Tank.
as you read through this, keep coming back to this.
In medical terms, the shed is your subcutaneous fat. The kitchen is your liver. The laundry room is your skeletal muscle. The bedroom is your pancreas. The car engine is your heart. The safe is your kidneys.
Each of these places can hold a little fat. None of them are designed to hold significant amounts. When they do, they break.
Why does this happen?
South Asian fat doesn’t end up in the wrong places by accident. It ends up there because the body has nowhere else to put it.
The Thrifty Engine substrate is real and quantified: about 34% less brown adipose tissue than Europeans, resting metabolic rate lower at the same body composition, and VO2max running about 22% lower than matched Europeans. Survival advantage in a world of food scarcity and physical movement. A trap in a world of caloric surplus and sedentary work.
Caloric surplus has three potential exits from the body. Burn it as ATP during exercise. Burn it as heat through brown fat or skin radiation. Store it safely in expandable subcutaneous fat.
For South Asians, all three doors are partly shut at once. Burning calories as ATP requires oxidative capacity we largely don’t have, compounded by sedentary diaspora work. Burning calories as heat requires brown fat we mostly don’t carry. Storing them safely requires subcutaneous capacity that hits its ceiling at lower BMI than Europeans.
So the surplus has to go somewhere. It goes everywhere it shouldn’t.
This is why “just eat less and move more” isn’t a complete answer for most South Asians. The mismatch is upstream of behavior. The biology is set up to push surplus into ectopic depots faster than other populations. Behavior matters, but so does understanding what we’re up against.
A Tour of the Wrong Places
Some of these you’ve heard of. Most you probably haven’t.
The Liver
Where Most of the Research Lives
Hepatic fat, what doctors call non-alcoholic fatty liver disease (NAFLD), now renamed MASLD, is the depot the field has studied the most, gaining further awareness post-GLP-1. About 30–40% of South Asians have fatty liver, and many at completely normal BMI. The definitive meta-analysis (Iliodromiti 2022) of over 7,000 patients found South Asian men have substantially more liver fat than matched White Europeans, the effect size is large and consistent.
Hepatic fat is bad in two ways.
It directly causes liver disease: fibrosis, cirrhosis, eventually liver cancer.
And it makes your liver insulin-resistant, which is what causes your fasting glucose to rise and your triglycerides to spike. The liver becomes a glucose factory that never closes.
The mechanism is more than “fat sitting in the liver.” When fatty-acid delivery and de novo lipogenesis exceed the liver’s ability to oxidize or export fat as VLDL, lipid intermediates build up inside hepatocytes. The best-studied culprit is diacylglycerol, which activates PKCε and blunts insulin signaling at the insulin receptor (Perry/Shulman 2014, PMID 24899308).
That’s why liver fat shows up clinically as the South Asian pattern we know too well: normal-ish BMI, high triglycerides, high ApoB, fasting glucose creeping upward, and ALT that may still sit inside the “normal” range.
A meaningful chunk of the SA hepatic-fat story is genetic. The PNPLA3 gene variant (rs738409-G) is present in about 30% of South Asians and dramatically amplifies hepatic fat at any insult. Fructose and refined carbs hit especially hard here because they feed hepatic de novo lipogenesis; ultra-processed oils may matter too, but the strongest evidence is still around substrate overload, insulin resistance, and genetic susceptibility.
The good news: hepatic fat is reversible. Even modest weight loss (5–10% of body weight) clears a substantial fraction. SGLT2 inhibitors, GLP-1 agonists, and the new MASH drug resmetirom all reduce hepatic fat. This is the depot we’re best at treating.
Visceral Fat
The Belly That Wasn’t There
Visceral fat is the commonly recognized, deep fat around your organs. It’s the fat your waist measurement is trying to estimate. South Asians accumulate it earlier, at lower BMI than Europeans, which is why our waist cutoffs are lower (≥90 cm men, ≥80 cm women instead of the 102/88 used for Europeans).
This is the fat that produces inflammatory cytokines (IL-6, TNF-α, MCP-1) that drive systemic inflammation and insulin resistance. But the key anatomical point is drainage.
Visceral fat is more than deeper subcutaneous fat. Much of it drains toward the portal circulation, meaning free fatty acids and inflammatory signals get delivered straight to the liver before the rest of the body ever sees them. That’s the classic “portal theory” of visceral adiposity: the belly depot talks directly to the organ that regulates fasting glucose, triglyceride production, and ApoB particle export.
So visceral fat is dangerous partly because of what it secretes, and partly because of where its plumbing goes. It is the fat that explains why a South Asian with a 35-inch waist can have the metabolic profile of a European with a 42-inch waist.
One honest perspective we have to keep in the framework: at the same BMI, South Asian visceral fat may not be dramatically higher than European visceral fat. Filipino women actually may even exceed us. Rather, the South Asian story is about threshold, we cross harmful waist cutoffs at lower BMI, more than absolute amount. Either way, the clinical message is the same: measure waist, not BMI. Waist-to-height ratio above 0.5 means trouble regardless of what the scale says.