Marketing/Growth thread by @lowmegatron

1

Releasing/burning more fat can
> Cause insulin resistance
> Ruin metabolism
> Ruin thyroid function
> Slow fat loss

Elevated free fatty acids, caused by “fat loss” diets, are also seen in cancer, T2D, obesity, and fatty liver.

Is this a good idea for long-term health?🧵

2

> Triglycerides are key
> Nearly all fat is stored in trigs
> Trigs = 3 fatty acids + glycerol
> Lipolysis breaks them apart
> Releases fatty acids + glycerol
> The main enzymes involved are ATGL, HSL, MGL

3

HSL is the most significant driver of above-baseline lipolysis

> HSL is increased by:
> Adrenaline/noradrenaline
> Glucagon
> Growth hormone
> Cortisol

> The main HSL inhibitor is insulin

4

Glycerol and free fatty acids are released by lipolysis
> Glycerol is a good proxy for free fatty acid levels
> Glycerol is increased by 50% in cancer/wasting

5

Free fatty acids are elevated in:
> Type 2 diabetes
> Obesity
> Insulin resistance
> Obesity is associated with "insulin resistance"
PMID: 36530555

6

The physiological link between obesity and insulin resistance must:

> Be elevated in the blood of obese people
> Raising it should increase insulin resistance
> Lowering it should decrease insulin resistance

Only free fatty acids meet all these criteria

7

> Increasing Free fatty acids (FFAs) causes insulin resistance

8

> Free fatty acids are elevated in obesity
> 61% higher baseline FFAs in obesity
PMID: 5806343

9

Elevated free fatty acids are driven by “stress”

↑Low-carb diets
↑Fight or flight
↑Fasting, exercise,
↑Psychological stress
↑Toxins, disease

PMID: 20107198

10

During long-term stress-induced increases in lipolysis/fat-burning:

> Fat loss can occur initially
> FFAs lower thyroid metabolism
> Fat loss slows/stops
> Metabolism is ruined

Master Metabolism@lowmegatron

“I keep exercising more and eating less but I can’t lose weight.”

> Thyroid hormone regulates the resting metabolic rate
> Resting metabolic rate burns calories at rest
> Thyroid hormone is regulated by energy availability

If calories IN are too low or calories OUT are too high (excessive exercise in relation to calories in)
↓ T3/fT3 (the thyroid hormone)
↑Reverse T3 (blocks the thyroid hormone)
Resting metabolic rate decreases

Increasing the metabolic rate promotes leanness and health. As thyroid function improves, calories are used for producing energy and sustaining health rather than being stored as excess fat.

“Reductions in T3 (16%) and fT3 (9%) occurred abruptly between 19.0 and 25.0 kcal/kg LBM-1.day-1 and that increases in fT4 (11%) and rT3 (22%) occurred abruptly between 10.8 and 19.0 kcal/kg LBM-1.day-1... If energy deficiency suppresses reproductive as well as thyroid function, athletic amenorrhea might be prevented or reversed by increasing energy availability through dietary reform to 25 kcal/kg LBM LBM-1.day-1, without moderating the exercise regimen.”

11

Elevated free fatty acids:

> Inhibit thyroid hormone conversion
> Inhibit thyroid hormone binding
> Cause stress-induced hypothyroidism

12

HSL drives stress-lipolysis

HSL-deficient mice have:
> Lower lipolysis/FFAs
> DECREASED fat accumulation
> Excess fat is not created...
> Because glucose oxidation is not impaired...

Otherwise:
> High FFAs cause metabolic damage
> Then FFAs get REINCORPORATED into fat

13

In mice, lowering lipolysis led to:

> Much less fat gain
> Less lipolysis -> less fat

"The reduced FFA production is counteracted by a drastic reduction of FFA reesterification (back into trigs)... These metabolic adaptations result in decreased fat mass..."
PMID: 12923228

14

Stimulating HSL in mice with a compound called isoproterenol

> Mimics stress-induced lipolysis
> 3-4x increase in fat gain

Compared to HSL knockout mice + isoproterenol
isoproterenol

15

Ketosis in obese men on isocaloric diets

> Ketosis increased lipolysis
> Ketosis increased fat burning
> Ketosis led to 49% increased weight loss
> Ketosis led to 45% LESS/ fat loss

[Daily avg. fat loss]

16

> 15 days non-ketosis - 5 kg fat loss
> 28 days ketosis - 5 kg fat loss

"The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure... The isocaloric ketogenic diet was not accompanied by increased body fat loss."

17

Insufficient sleep is a stress

> It increases lipolysis
> It increases free fatty acids
> It lowers "insulin sensitivity"

Master Metabolism@lowmegatron

Any kind of stress can increase free fatty acid levels (NEFA) causing metabolic disturbance.

“Sleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels.”

PMID: 25702040

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In NAFLD (fatty liver)

> 59% of liver fat comes from free fatty acids
> 15% comes from dietary fat
> Only 26% comes from glucose

> Lipolysis is elevated by 50%
> Liver production of sugar +30%

19

Lipid peroxidation is the breakdown of PUFAs, unstable fatty acids from seed oils, etc.

> Lipid peroxidation byproducts are inflammatory
> Lipid peroxidation drives many chronic diseases

20

Diseases involving lipid peroxidation:
> Type 2 diabetes
> Obesity
> Atherosclerosis
> Hypertension
> Colon cancer
> Breast cancer
> Heart failure
> Alzheimer's disease
> Parkinson's disease
> Huntington's disease
> Fatty liver disease
> COPD
> Asthma
> Pulmonary fibrosis
> Rheumatoid arthritis
> Systemic lupus erythematosus
> Liver cancer
> Cataracts
> Macular degeneration
> Chronic kidney disease

21

> Lipid peroxidation is much more likely when fatty acids are free
> Increasing lipolysis normally increases lipid peroxidation

22

To minimize lipolysis, free fatty acids and lipid peroxidation

Optimize Blood Sugar:
> When blood sugar is optimal, insulin inhibits lipolysis
> When blood sugar levels drop, stress hormones stimulate lipolysis
> Stress increases lipolysis, but carbohydrates reduce the stress-induced increase

Reduce membrane lipid hydrolysis, another source of free fatty acids:
> Vitamin E
> Benfotiamine
> Optimize thyroid hormone (T3)
> ↓ Estrogen & NO
> Fix leaky gut/endotoxin
> Limit omega-3s
> Omega-3 ↑PLA2 enzyme that triggers membrane hydrolysis

Minimizing lipid peroxidation:
> Decrease PUFA consumption
> Increase saturated fat to PUFA ratio
> Vitamins E and C
> Coffee
> Rosemary
> Vitamin A
> Taurine
> Coconut oil
> L-theanine
> Zinc
> Low dose aspirin

23

H/t Jay Feldman Wellness, whose recent video on lipolysis was helpful in researching some of this thread. Check out his excellent YT channel.

                            24
                        
Some things NOT implied in this thread:
> All stress is to be avoided
> Exercise is to be avoided 
> Keto/low carb doesn’t cause fat loss
> Fasting doesn’t cause fat loss
> Lipolysis must be brought to zero

Releasing/burning more fat can > Cause insulin resistance > Ruin...

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