🔥 Lose fat
6 mechanistic pathways · 95 options
Fat loss is not one mechanism, and that is why people stall. An appetite drug does nothing for someone who already eats little and has a dead metabolic rate; a mitochondrial uncoupler does nothing for someone who cannot stop eating at 9pm. Find the pathway that matches your actual failure point, then pick from inside it.
The pathways
Appetite & satiety signalling
Incretin and amylin receptors in the hypothalamus and brainstem set how much food it takes to feel done, and how fast the stomach empties. Engage them and intake falls without willpower being involved. This is the most clinically developed pathway in the whole Vault — and the least interesting one if your intake is already low.
Mitochondrial & metabolic reprogramming
This is the pathway Cam means when he says stretch and extrapolate. Instead of eating less, you change how much energy the cell burns and how efficiently it burns it — mitochondrial biogenesis, uncoupling, NAD+ availability, PGC-1α. Almost nothing here has a human fat-loss trial. The mechanisms are well characterised and the rodent data is often striking. That gap is the opportunity and the risk in one.
Direct lipolysis & adrenergic drive
Skip the brain and the mitochondrion and act on the fat cell itself. β-adrenergic receptors on adipocytes trigger hormone-sensitive lipase; GH fragments do something similar without the glucose consequences of full GH. Fast-acting, and the same receptors sit on your heart, which is the entire safety story of this pathway.
Substrate partitioning & insulin control
Where a calorie goes matters as much as how many arrive. Chronically elevated insulin keeps hormone-sensitive lipase switched off — you cannot mobilise fat you are simultaneously storing. Improve glucose disposal and you change the destination of the same food.
Thyroid & thermogenic substrate
Thyroid hormone sets the floor under resting metabolic rate. If that floor has dropped — from dieting, from illness, from age — no amount of appetite suppression fixes the arithmetic. This pathway is about the denominator, and it is the one most worth testing before treating.
Lean-mass protection while cutting
Fat loss that takes muscle with it lowers your metabolic rate and guarantees the regain. Any aggressive deficit — and every GLP-1 — needs an answer to this, and it belongs in the fat-loss plan rather than as an afterthought once the scale has moved.
Test before you choose a pathway
Every route below can be argued for on mechanism. Only bloodwork tells you which one is actually your problem — and picking the wrong pathway is the most common reason someone concludes "none of this works". Across all 6 pathways, these are the 21 markers worth having in front of you first.
Ordered together:
📉 Insulin Resistance Deep Dive🍭 Metabolic Health & Prediabetes🌡️ Adrenal & Cortisol Axis🦋 Thyroid — First Look💉 On a GLP-1 (Semaglutide / Tirzepatide)You have the pathways. Here is the stack.
The Fat Loss Blueprint names the one compound I would start with in each of these 6 pathways, what it was chosen over, and why — plus 20 options to swap in or stack on top, every one of them priced and linked.
Open The Fat Loss Blueprint →The protocols behind these
Dosing, stacking and cycle timing live inside the Academy, alongside the full interactive Vault and the Bloodwork Protocols.
Join the Academy — $10/mo →← Open Lose fat in the interactive Vault · All 21 goals
Frequently asked questions
This goal is broken into 6 distinct mechanistic pathways — Appetite & satiety signalling; Mitochondrial & metabolic reprogramming; Direct lipolysis & adrenergic drive; Substrate partitioning & insulin control and others — across 95 compounds and supplements. Each pathway is a different argument about how the body gets there, so the useful question is which one matches where you are actually stuck.
The one that matches your actual limitation, which bloodwork usually settles faster than guessing. An appetite drug does nothing for someone who already undereats, and a thyroid intervention does nothing if your thyroid is fine. Each pathway page lists the markers that tell you whether it is your problem.
No. The 6 pathways are listed in mechanistic order, not by strength of evidence, and neither are the 95 options inside them. A lot of what works in this space has never had the trial run, and sorting by trial count would bury exactly the compounds you came looking for.