Brad Marshall

Lactate and the Lipoic Acid Flu, An Hypothesis and n=1

In my last post I recommended a strategy of combining lipoic acid – a natural, mitochondrially produced substance which oxidizes NADH to NAD+ – and succinate, which drives mitochondrial ROS production and oxidation of NADH to NAD+ via the activity of the enzyme NNT. Both of these are designed to shift the redox pool of …

Lactate and the Lipoic Acid Flu, An Hypothesis and n=1 Read More »

Obesity as a Global Succinate Dehydrogenase Activity Deficit – The ROS Theory of Obesity Part III, Part 2

I’m using the word global to mean “in all tissues of the body” but I’d forgive you if you thought that I meant “in all countries where they eat vegetable oil”. Either way, really. As I explained in part 1, the production of mitochondrial ROS is a thermogenic loop that wastes calories as heat.  If …

Obesity as a Global Succinate Dehydrogenase Activity Deficit – The ROS Theory of Obesity Part III, Part 2 Read More »

Sandra’s Story

I told the story of Sandra in Obesity as a Global Succinate Dehydrogenase Activity Deficit. I asked her to be a guinea pig and she was happy to share data. This is her story of her n=1 trial using Succin-ade for a month. The “supplements” she mentions and vitamin D3 and K2 plus the polyphenols …

Sandra’s Story Read More »

ROS as a NAD+ Regenerating, Thermogenic Cycle – The ROS Theory of Obesity Part III, Part 1

On this blog I have argued that: The traditional French diet combining starch and saturated fat results in leanness The richest, least active American men stayed lean on 4500 calories per day in the 1930s Metabolic rate is correlated to saturation level Obese humans have very unsaturated body fat The metabolic rates of Americans dropped …

ROS as a NAD+ Regenerating, Thermogenic Cycle – The ROS Theory of Obesity Part III, Part 1 Read More »

Reduce SIRT1 and AMPK activity with low-fat calorie restriction, Increase them with high-fat feasting!

In the last article we saw that a deficiency in AMPK and SIRT1 activity leads to the inactivation of the mitochondrial SIRT3 deacetylase, acetylated (turned off) mitochondrial enzymes and low metabolic rate. I suggested at the end that to escape this pattern, you have to activate AMPK and SIRT1 at the same time. In this …

Reduce SIRT1 and AMPK activity with low-fat calorie restriction, Increase them with high-fat feasting! Read More »

You’re fat because your mitochondrial enzymes are acetylated

I’ve been working on this mega post that was getting too long and complicated.  I decided to break it into three or four parts and start at what was going to be the end.  I’m feeling really excited about this series of posts because I feel like we’re really getting to the root causes of …

You’re fat because your mitochondrial enzymes are acetylated Read More »

AMPK Causes Insulin-independent glucose uptake in muscle tissue

The way that insulin decreases blood glucose is by causing the translocation of a glucose transporter called GLUT4 (GLUcose Transporter 4) from vesicles (little pockets) inside the cell to the cell membrane where it transports glucose into the cell.  GLUT4  is said to be “insulin dependent”.  When glucose levels inside of cells are high, glycogen …

AMPK Causes Insulin-independent glucose uptake in muscle tissue Read More »

“The Fat Pigs”, FIAB Podcast, Episode 2!

Fire In A Bottle, The Podcast episode 2 is out! In this episode I focus on the paper referenced in my post about Ossabaw pigs moving from pathological insulin sensitivity to torpor. I also reference my post about linoleic acid accumulation predicting low diabetes risk. Lastly, I talk about the EPIC Potsdam study that predicts …

“The Fat Pigs”, FIAB Podcast, Episode 2! Read More »

Vitamin D is a nuclear receptor superfamily member that activates AMPK

Vitamin D is the sunshine vitamin.  When sunshine hits your skin, your body uses the UV rays to convert cholesterol into vitamin D.  A theme of this blog has been that obese humans have a torpid metabolism evolutionarily linked to that of hibernating animals in winter.  As autumn approaches, consumption of foods high in linoleic …

Vitamin D is a nuclear receptor superfamily member that activates AMPK Read More »

Campari is a dual bile acid receptor agonist that activates AMPK

I am a huge fan of Italian bitter liqueurs.  I was first introduced to the idea when I was working at Memorial Sloan-Kettering in Manhattan.  A co-worker brought in a six pack of bitter soda from a local pizza place.  I took a sip.  It was revolting.  My only thought was, “this tastes like bile!  …

Campari is a dual bile acid receptor agonist that activates AMPK Read More »

AMPK is activated by HIGH cellular energy after a starchy meal

AMPK is a key regulator of metabolic rate and fat burning.  The mainline thinking on AMPK often follows the puritanical view of classic obesity research:  AMPK senses LOW cellular energy levels by monitoring the ratio of ATP to ADP and AMP.​1​   This suggests that the best way to stimulate AMPK is by reducing caloric intake.  …

AMPK is activated by HIGH cellular energy after a starchy meal Read More »

SCD1 Regulates AMPK and AMPK Regulates SCD1

So like I was saying, biology is weird.  AMPK and SCD1 are a literal teeter totter. When SCD1 goes up, AMPK goes down.  When AMPK goes up, SCD1 goes down. This matters because, as I pointed out in the last post, AMPK can help to keep us out of torpor. In hibernating animals and obese …

SCD1 Regulates AMPK and AMPK Regulates SCD1 Read More »

AMPK is Kryptonite to the Nuclear Receptor “Superfamily”

Summary  Activating AMPK in the livers of mice prevents diet induced obesity despite higher caloric consumption Mice with activated AMPK have lower levels of cytochrome P450 enzymes that produce 12-HETE and 15-HETE – specific activators of PPAR gamma Mice with activated AMPK have higher rates of both fat and glucose metabolism AMPK blocks the pathway …

AMPK is Kryptonite to the Nuclear Receptor “Superfamily” Read More »

Announcing Fire In A Bottle, The Podcast!

That’s right, Brad has a podcast now. In the first episode he tells the story of the squirrel and the acorn, what makes acorns so uniquely fattening and how Native Americans knew to avoid acorn oil! And it’s funny! Available on Spotify, Apple Podcasts or wherever you listen to podcasts.

The AhR is the Keymaster to Torpor

My last posts were viewed by some as pessimistic in a “once you’re obese, you are stuck” kind of way.  I don’t believe that and very soon I will start writing about solutions.  Having said that, this post will perhaps seem pessimistic if you thought the previous ones were.  I’m working through the basic mechanisms …

The AhR is the Keymaster to Torpor Read More »