Genetics associated with increased 11β-HSD1 expression?

[Mazzle]

This post exactly describes my dilemma.

Exercise + Fasting Is Stress, Causes Obesity And IR, And Requires Cortisol Blockade To Reverse

I think this thread will ring true for all people who at some in their lives exercised in order to lose weight. Just like fasting, it works great in younger age (

raypeatforum.com

(CHAT GPT )- Several genetic variations (polymorphisms) that have been associated with 11β-HSD1 expression, and some of these can be identified through genetic testing like 23andMe.
One such variant is the rs846910 single nucleotide polymorphism (SNP), which is located in the HSD11B1 gene that encodes for 11β-HSD1. The rs846910 SNP has been associated with increased 11β-HSD1 activity and has been linked to increased risk of metabolic disorders such as type 2 diabetes and obesity.
Another variant is the rs12086634 SNP, which is located in the HSD11B1 gene. This SNP has also been associated with increased 11β-HSD1 activity and increased risk of metabolic disorders.

23andme - I have the g/g genotype for rs846910 I have the g/t genotype for rs12086634
(CHAT GPT) Studies have shown that individuals with the G/G genotype for rs846910 have higher levels of 11β-HSD1 activity compared to those with the A/A or A/G genotype. This higher level of activity is associated with an increased risk of metabolic disorders such as obesity, insulin resistance, and type 2 diabetes. Studies have shown that individuals with the G allele for rs12086634 have higher levels of 11β-HSD1 activity compared to those with the T allele. This higher level of activity is associated with an increased risk of metabolic disorders such as obesity, insulin resistance, and type 2 diabetes.

This study seems to back CHATGPT up Association between Selected Polymorphisms rs12086634, rs846910, rs4844880, rs3753519 of 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) and the Presence of Insulin Resistance in the Polish Population of People Living in Upper Silesia

Association between Selected Polymorphisms rs12086634, rs846910, rs4844880, rs3753519 of 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) and the Presence of Insulin Resistance in the Polish Population of People Living in Upper Silesia​

My father died young of diabetes and heart complications, and all my sisters and mother are very overweight and have some sort of metabolic disorder. The wider family, as a whole, are slim.

Does anyone have any 11β-HSD1 inhibitors for rats such as the ones CHAT GPT suggest @haidut ?
CHATGPT - There are several medications that act as selective 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors, including:

1. AZD4017: This medication is an oral inhibitor of 11β-HSD1 that has been shown to improve insulin sensitivity and reduce body weight in animal models.
2. INCB13739: This medication is an oral inhibitor of 11β-HSD1 that has been shown to improve glucose control and reduce body weight in animal models.
3. MK-0916: This medication is an oral inhibitor of 11β-HSD1 that has been shown to improve glucose control and reduce body weight in animal models.
4. BVT.2733: This medication is a selective 11β-HSD1 inhibitor that has been shown to improve glucose control and reduce body weight in animal models.
   • Resveratrol: This is a polyphenolic compound found in grapes, red wine, and berries. It has been shown to have a variety of health benefits, including potential anti-inflammatory and anti-obesity effects. Studies suggest that resveratrol may also act as a selective 11β-HSD1 inhibitor and could potentially help to improve glucose control and reduce the risk of metabolic disorders.
   • Epigallocatechin gallate (EGCG): This is a polyphenolic compound found in green tea. It has been shown to have antioxidant, anti-inflammatory, and anti-obesity effects. Studies suggest that EGCG may also act as a selective 11β-HSD1 inhibitor and could potentially help to improve glucose control and reduce the risk of metabolic disorders.
   • Curcumin: This is a polyphenolic compound found in turmeric. It has been shown to have antioxidant, anti-inflammatory, and anti-obesity effects. Studies suggest that curcumin may also act as a selective 11β-HSD1 inhibitor and could potentially help to improve glucose control and reduce the risk of metabolic disorders.

What do you think would be the best bet going forward to block that pesky 11β-HSD1

ps....progesterone does nothing for me, makes me feel unwell and ends up causing weight gain

 

[maillol]

Bump. I also have this genotype.

 

[Jamsey]

Coffee
Emodin
Aspirin
Vitamin A retinol
Niacinamide
palmitic acid/ saturated fat

The links for these should be below if you scroll down.

But if the goal is resolving or preventing metabolic disorder, then anything that lowers free fatty acids and promotes glucose oxidation will help. So on the most simple level, this means eating carbs often to minimize free fatty acid release. For a macro nutrient basis, this means prioritizing
-protein with lower levels of methionine, tryptophan, cysteine and BCAAs
- fat with lower levels of polyunsaturated fats and higher saturated fats
- carbs in the form of sugar instead of starch(though this distinction is not as important as just eating well digested carbs often)

It helps to eat low fat / low protein(~50g) or just low BCAA(<8g) / high carb, give blood, engage in low impact exercise, and not worry about genes. On this forum, we tend to believe in epigenetics, or the idea that environment and behavior can affect and control genetic expression.

For some good info on metabolic disorders, read this website Fire In A Bottle