2/ Also, it's all very mechanistic, with ANGPTL4 vs. 3/8 being oppositely regualted by feeding and fasting in a tissue specific manner such that fasting decreases fat storage in adopicytes and feeding promotes it.
And, perhaps, unsuprislingly, the lipid metabolism is...
3/ w.r.t ANGPTLs (and specifically 4, which controls local LPL activity) is linked with glucose homeostasis...
4/ Also, exercise locally induces ANGPTL4 in adipocytes so as to direct fat fuel to working muscles.
The Peptide Proven to Cut Visceral Fat (In RCTs) 🧵
1/6) There is a peptide proven in multiple double-blinded, placebo-controlled randomized controlled trials to reduce visceral fat.
It’s called tesamorelin. (link at the end)
2/6) Tesamorelin is an analog of growth hormone–releasing hormone, a hormone released by the brain that signals the pituitary to release growth hormone.
Its main advantage over growth hormone is that it stimulates the body’s natural release of growth hormone, rather than adding a non-physiologic dose that doesn’t align with biological rhythms.
3/6) To give you just a taste of data: in a landmark 2007 New England Journal of Medicine study, patients with HIV on antiretroviral therapy and excess abdominal fat were given 2 mg of tesamorelin or placebo for 26 weeks.
Visceral fat decreased by ~15% in the tesamorelin group, while it increased in the placebo group. Subcutaneous fat did not change, and there was no loss in lean mass.
*Nuance note: Historically, the patient population studied has been patients with HIV taking antiretroviral therapy. Why? These therapies can cause visceral fat gain. So these patients aren’t biologically unique to HIV—they’re just a particularly vulnerable population in which these drugs have been assessed and FDA-approved.
After 7 Years, I Changed My Mind on Cholesterol Meds (Or Did I?)
🚨You'll want to read this one all the way though. Link at the end🚨
1/7) After seven years of living with astronomically high cholesterol, I’ve decided to start two medications. Not statins, but ezetimibe and bempedoic acid.
But that’s NOT the real story. The real story is WHY… and it has nothing to do with cholesterol🤨🤔...
Quick preface: “cholesterol-lowering drugs” are named for one effect, not their full biological impact.
Molecules don’t respect our labels. These drugs can influence multiple systems, including metabolism and brain health.
And in this case, they likely do.
2/7) Take ezetimibe. Beyond lowering LDL, evidence suggests it crosses into the brain and influences neurobiology.
Specifically, is disrupts the interaction between 14-3-3 and hexokinase, reducing protein aggregation.
Full video:
3/7) That means less amyloid, less tau, and even improved autophagy.
Even more interesting: retrospective analyses have found up to an ~8x lower risk of Alzheimer’s in patients on ezetimibe.
Not causal. Not definitive. But a signal worth paying attention to—especially in the right context.
1/5) Here are four things statins do in your body.
First: A human controlled trial found statins reduced GLP-1 levels by 50% in 16 weeks.
The clinical implications aren’t fully clear—but the fact this isn’t discussed is a disservice to science and to patients.
2/5) Statins disrupt mitochondrial function.
They reduce CoQ10 synthesis (a key electron carrier) and directly inhibit Complex IV in the electron transport chain. These are biochemical effects—but they matter for informed decisions. staycuriousmetabolism.substack.com/p/the-mitochon…
3/5) Statins are sexist. Women face higher risk of muscle pain, potential muscle loss, and statin-induced diabetes.
Eating 1000 Sardines Gave Me THIS Superpower
(New 2026 Findings!)
1/8) I ran a self-experiment where I ate 1000 sardines in a month.
Sure, it made me stink—but it also gave me one epic superpower. Let me explain. 🧵 (link at the end)
We all know sardines make your breath stink and that they’re nutrient-dense.
That’s basic.
But eating that many sardines changed me. It gave me a “superpower” that had my inner Marvel nerd activated—and my scientist brain scrambling to explain it.
Eventually, I found those data.
2/8) It was new paper in a top journal turned confusion into clarity and left me in awe of how much we’re still uncovering about human physiology.
1/5) One meta-analysis of controlled human trials found that citrus bergamot extract lowers triglycerides, increases HDL, and lowers LDL — to a substantial degree.
But that’s not all... (link at the end)
2/5) More interestingly, one trial showed that while bergamot decreased small dense LDL, it increased‘large, fluffy’ LDL.
This shift towards a preponderance of large LDL vs small LDL is a metabolic fingerprint of improved metabolic health.
3/5) So how does citrus bergamot work?
Citrus bergamot isn’t a single nutrient — it’s a cocktail of polyphenolic compounds that influence multiple metabolic enzymes.
For example, the bergamot polyphenols inhibit the enzyme ACAT, contributing to downstream increase LDL receptor expression.