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11beta-HSD1

Related Topics:

• diabetes / syndrome x / hypertension / HDL cholesterol / triglycerides / obesity / weight control / cortisol / pot bellies / memory loss / Alzheimer's

News & Research:

• Vitamin D pill a day may improve exercise performance and lower risk of heart disease - Science Daily, 11/1/15 - "Previous studies suggest that vitamin D can block the action of enzyme 11-βHSD1, which is needed to make the "stress hormone" cortisol. High levels of cortisol may raise blood pressure by restricting arteries, narrowing blood vessels and stimulating the kidneys to retain water. As Vitamin D may reduce circulating levels of cortisol, it could theoretically improve exercise performance and lower cardiovascular risk factors ... gave 13 healthy adults matched by age and weight 50μg of vitamin D per day or a placebo over a period of two weeks ... Adults supplementing with vitamin D had lower blood pressure compared to those given a placebo, as well as having lower levels of the stress hormone cortisol in their urine. A fitness test found that the group taking vitamin D could cycle 6.5km in 20 minutes, compared to just 5km at the start of the experiment. Despite cycling 30% further in the same time, the group taking vitamin D supplements also showed lower signs of physical exertion" - See vitamin D at Amazon.com.
  • Converting between IU and mg/mcg - 50 mcg = 2000 IU of vitamin D.
  • While on the subject of cortisol, I was ordering a supply of deprenyl a.k.a. selegiline the other day that I've been taking for years for anti-aging and an article said that it also reduced cortisol as an additional benefit.  I researched it and came up with this:
    • Cortisol is higher in parkinsonism and associated with gait deficit - Acta Neurol Scand. 1998 Feb;97(2):77-85 - "Selegiline was associated with a lower cortisol" - See deprenyl (selegiline) at International Anti-aging Systems.
• Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients - Metabolism. 2011 Jun 23 - "11-β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5α- and 5β-reductases ... Forty-one patients were recruited (age, 41.8 +/- 10.6 years; body mass index, 42.1 +/- 6.6 kg/m(2); 71% women). The expression of hepatic 5α- and 5β-reductases was positively correlated (r = +0.53, P = .004), and their expression levels were correlated with hepatic 11β-HSD1 expression (r = +0.61, P < .001 for 5α-reductase and r = +0.50, P < .001 for 5β-reductase). Hepatic 5α-reductase was associated with insulin (r = +0.34, P = .015). Visceral adipose tissue 11β-HSD1 expression was associated with glucose (r = +0.37, P = .025) and insulin (r = +0.54, P = .002). Our results showed that 5α-reductase and VAT 11β-HSD1 expressions were associated with insulinemia. These findings suggest that overexpression of 5α-reductase, through a higher inactivation of cortisol in the liver, could have a protective role in preserving hepatic sensitivity to insulin. The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11β-HSD1 to avoid systemic hypercortisolism"
• Older age memory loss tied to stress hormone receptor in brain - Science Daily, 4/6/11 - "one receptor was activated by low levels of cortisol, which helped memory. However, once levels of this stress hormone were too high they spilled over onto a second receptor. This activates brain processes that contribute to memory impairment ... high levels of the stress hormone in aged mice made them less able to remember how to navigate a maze. The memory recall problem was reversed when the receptor linked to poor memory was blocked ... lowering the levels of these stress hormones will prevent them from activating a receptor in the brain that is bad for memory ... The researchers are currently investigating a new chemical compound which blocks an enzyme -- 11beta-HSD1 -- that is involved in producing stress hormones within cells"
• Errant Enzyme Causes Big Bellies - WebMD, 12/11/01 - "They looked at an enzyme called 11-beta hydroxysteroid dehydrogenase type 1. This enzyme is able to increase the level of cortisol in fat cells without raising the level of cortisol in the blood ... The researchers genetically engineered mice that overproduce this enzyme. They made sure that the level of the enzyme was equivalent to the level previously found in the fatty tissue of overweight humans. As expected, the mice produced extra amounts of cortisol in their fat cells, but not in their blood ... The next step was to compare these mice to mice that produced normal amounts of the enzyme. Even when fed a low-fat diet, the genetically-altered mice developed a pot belly while the normal mice did not. The problem was even worse when the altered mice were fed a high-fat diet ... We were surprised to find that it took only a modest increase in this enzyme to cause the mice to become ... obese"
• Single enzyme to blame for potbellies: study - MSNBC, 12/6/01 - "What they found was that a single enzyme in fat cells that raises levels of cortisol — the “fight or flight” stress hormone — triggers fat accumulation around the belly and its associated ill effects ... The researchers were drawn to the role of cortisol because patients with a rare illness known as Cushing syndrome — who have too much of the steroid hormone in their blood — develop severe obesity concentrated around their middles and become diabetic ... Since overweight people without Cushing syndrome typically don’t have too much cortisol in their bloodstreams, Flier hypothesized that they may be producing high cortisol levels solely in their fat cells — possibly because the enzyme HSD-1, which makes cortisol from an inactive molecule, is overactive ... The level of cortisol in their stomach fat tissue was 15 percent to 30 percent higher than in their non-engineered counterparts"

Abstracts:

• 11β-HSD1 Inhibitor Alleviates Non-Alcoholic Fatty Liver Disease by Activating the AMPK/SIRT1 Signaling Pathway - Nutrients 2022 Jun 6 - "We investigated the effect of an 11β-HSD1 inhibitor (H8) on hepatic steatosis and its mechanism of action. Although H8, a curcumin derivative, has been shown to alleviate insulin resistance, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown ... Our findings demonstrate that H8 alleviates hepatic steatosis, by inhibiting 11β-HSD1, which activates the AMPK/SIRT1 signaling pathway" - See curcumin at Amazon.com.
• Metformin increases cortisol regeneration by 11βHSD1 in obese men with and without type 2 diabetes mellitus - J Clin Endocrinol Metab. 2016 Jul 26 - "Metformin increases whole body cortisol generation by 11βHSD1 probably through an indirect mechanism, potentially offsetting other metabolic benefits of metformin"
• Vitamin A Decreases Pre-receptor Amplification of Glucocorticoids in Obesity: Study on the Effect of Vitamin A on 11beta-Hydroxysteroid Dehydrogenase Type 1 Activity in Liver and Visceral Fat of WNIN/Ob Obese Rats - Nutr J. 2011 Jun 23;10(1):70 - "11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11beta-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129mg/kg diet) on 11beta-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats ... Control groups received stock diet containing 2.6mg vitamin A/kg diet, where as experimental groups received diet containing 129mg vitamin A/Kg diet for 20 weeks ... Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11beta-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11beta-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein alpha(C/EBPalpha), the main transcription factor essential for the expression of 11beta-HSD1, decreased in liver by vitamin A fed-obese rats, but not in lean rats. Liver X receptor alpha (LXR alpha), a nuclear transcription factor which is known to downregulate 11beta-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes" - Note:  11beta-HSD1 goes hand in hand with cortisol.
• Promising drug candidate reverses age-related memory loss in mice - Science Daily, 10/12/10 - "Such memory loss has been linked with high levels of 'stress' steroid hormones known as glucocorticoids which have a deleterious effect on the part of the brain that helps us to remember. An enzyme called 11beta-HSD1 is involved in making these hormones and has been shown to be more active in the brain during aging ... We found that life-long partial deficiency of 11beta-HSD1 prevented memory decline with aging. But we were very surprised to find that the blocking compound works quickly over a few days to improve memory in old mice suggesting it might be a good treatment for the already elderly ... We previously showed that carbenoxolone, an old drug that blocks multiple enzymes including 11beta-HSD1, improves memory in healthy elderly men and in patients with type 2 diabetes after just a month of treatment, so we are optimistic that our new compounds will be effective in humans. The next step is to conduct further studies with our preclinical candidate to prove that the compound is safe to take into clinical trials, hopefully within a year"
• Dietary fatty acid composition alters 11beta-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue - Lipids Health Dis. 2010 Oct 8;9(1):111 - "The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Adipose-specific overexpression of 11beta-HSD1 induces metabolic syndrome in mice, whereas 11beta-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11beta-HSD1 gene expression in rat retroperitoneal adipose tissue. 11beta-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-alpha (C/EBP-alpha), the main transcription factor required for the expression of 11beta-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11beta-HSD1 by altering C/EBP--gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome" - Note:  11beta-HSD1 goes hand in hand with cortisol.
• Cerebrospinal Fluid Corticosteroid Levels and Cortisol Metabolism in Patients with Idiopathic Intracranial Hypertension: A Link between 11{beta}-HSD1 and Intracranial Pressure Regulation? - J Clin Endocrinol Metab. 2010 Sep 8
• Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice - Br J Pharmacol. 2010 Sep;161(1):113-26 - "11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an attractive therapeutic target of type 2 diabetes and metabolic syndrome. Emodin, a natural product and active ingredient of various Chinese herbs, has been demonstrated to possess multiple biological activities ... Emodin is a potent and selective 11beta-HSD1 inhibitor with the IC(50) of 186 and 86 nM for human and mouse 11beta-HSD1, respectively. Single oral administration of emodin inhibited 11beta-HSD1 activity of liver and fat significantly in mice. Emodin reversed prednisone-induced insulin resistance in mice, whereas it did not affect dexamethasone-induced insulin resistance, which confirmed its inhibitory effect on 11beta-HSD1 in vivo. In DIO mice, oral administration of emodin improved insulin sensitivity and lipid metabolism, and lowered blood glucose and hepatic PEPCK, and glucose-6-phosphatase mRNA. CONCLUSIONS AND IMPLICATIONS This study demonstrated a new role for emodin as a potent and selective inhibitor of 11beta-HSD1 and its beneficial effects on metabolic disorders in DIO mice. This highlights the potential value of analogues of emodin as a new class of compounds for the treatment of metabolic syndrome or type 2 diabetes" - Note:  (11beta-HSD1) goes hand in hand with cortisol.  It seems like what came first, the chicken or the egg.  I googled emodin and didn't see any reliable places that sold it.  One article said that it was in some resveratrol products and that the emodin was what caused the stomach problems.
• Lack of regulation of 11{beta}-hydroxysteroid dehydrogenase type 1 during short term manipulation of growth hormone in patients with hypopituitarism - Eur J Endocrinol. 2009 Jun 23
• Antidiabetic effects of 11beta-HSD1 inhibition in a mouse model of combined diabetes, dyslipidaemia and atherosclerosis - Diabetes Obes Metab. 2009 Jul;11(7):688-99 - "Importantly, 11beta-HSD1 inhibition leads to improved glucose metabolism and does not result in a worsening of atherosclerotic lesion area, yet retained antidiabetic potential in the face of multiple severe metabolic aberrations. This study reinforces the potential use of 11beta-HSD1 inhibitors in patients with the metabolic syndrome without negatively impacting atherosclerosis"
• Rosiglitazone decreases 11beta-hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue - Clin Endocrinol (Oxf). 2007 Jun 6 - "Part of the beneficial effects of rosiglitazone may be mediated by a reduction in the 11beta-HSD1 mRNA expression and activity in subcutaneous abdominal fat"
• Cortisol-cause and cure for metabolic syndrome? - Diabet Med. 2006 Dec;23(12):1281-8 - "reducing cortisol action may provide a novel therapeutic approach in the metabolic syndrome. There is substantial evidence that circulating cortisol concentrations are higher in people with hypertension and glucose intolerance ... Promising preclinical data suggest that novel 11beta-HSD1 inhibitors will have a role in lowering intracellular cortisol levels as a treatment for the metabolic syndrome"
• GH effect on enzyme activity of 11{beta}HSD in abdominal obesity is dependent on treatment duration - European Journal of Endocrinology, Vol 154, Issue 1, 69-74
• Obesity and cortisol status - Horm Metab Res. 2005 Apr;37(4):193-7 - "Tissue hypercortisolism, due to increased intracellular activity of 11beta-HSD-1, which catalyzes reduction of cortisone to cortisol, has been reported in obese mice and humans"
• Low-Dose Growth Hormone Inhibits 11beta-Hydroxysteroid Dehydrogenase Type 1 but Has No Effect upon Fat Mass in Patients with Simple Obesity -J Clin Endocrinol Metab 2003 May;88(5):2113-8 - "Although GH treatment significantly raised IGF-I, we were unable to demonstrate significant differences in body composition or metabolic profiles between GH- and placebo-treated groups. In addition, there was no alteration in total fat mass over time in the GH-treated group ... However, in comparison with baseline values, systolic blood pressure increased (119 +/- 3 vs. 130 +/- 4 mm Hg, P < 0.05 vs. baseline) and serum F/E ratio decreased (6.1 +/- 0.5 vs. 3.9 +/- 0.5, P < 0.05 vs. baseline) in the GH-treated group only ... Treatment with low-dose GH in obesity fails to alter fat mass despite a significant elevation in IGF-I and a shift in the global set point of E to F conversion consistent with inhibition of 11beta-HSD1" - I think it's saying that it reduced the active form of cortisol by a third.  That sounds like a big plus in itself.
• Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1 - J Med Chem 2002 Aug 29;45(18):3813-5
• Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism - J Clin Endocrinol Metab 2002 Nov;87(11):4984-90 - "Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E)"
• Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta -hydroxysteroid dehydrogenase type 1 expression and activity - J Biol Chem. 2001 Apr 20;276(16):12629-35. Epub 2001 Jan 22 - "treatment of diabetic db/db mice with rosiglitazone inhibited expression of 11beta-HSD-1 in adipose tissue. This decrease in enzyme expression correlated with a significant decline in plasma corticosterone levels. In sum, these data indicate that some of the beneficial effects of PPARgamma antidiabetic agents may result, at least in part, from the down-regulation of 11beta-HSD-1 expression in adipose tissue"
• 11beta-hydroxysteroid dehydrogenase type 1 (11beta HSD1) is expressed in human brain: inhibition with carbenoxolone improves cognitive function in healthy elderly men - "Inhibition of 11beta-HSD1 therefore provides an exciting new therapeutic target to prevent/ameliorate age-associated cognitive dysfunction in humans"