Life Extension Magazine®
Obesity is a major threat to longevity and health.
In addition to physically burdening the body’s structure, fat cells accelerate disease risk and aging. They do this by churning out enormous amounts of inflammatory factors.1
Quercetin is a bioactive flavonoid found in onions, apples, and other botanical sources.
In an animal study published in 2018, quercetin was shown to prevent obesity, while also offsetting the damaging effects of excess fat tissue.
With more than 2 in 3 adults considered overweight or obese,2 these new results show that quercetin may represent a defense against the age-accelerating consequences of excess fat.
What you need to know
In addition to physically burdening the body’s structure, fat cells accelerate disease risk and aging. They do this by churning out enormous amounts of inflammatory factors. Researchers have discovered that quercetin may offer protection against the deleterious damage caused by excess fat and may help prevent diet induced obesity.
The Dangers of Excess Fat
Obesity imposes grave risks on our health, especially as we age.
It increases the wear and tear on all body systems and raises blood lipid levels.
It also has ongoing effects that are less visible yet are more life-threatening.
When fat cells (adipocytes) and fat storage sites (adipose tissue) increase in size, an environment of insufficient oxygen supply (hypoxia) sets in, leading to cellular and biochemical changes.3
For example, hypoxia alters how fat cells express their genes, with the ultimate development of system-wide inflammation.4
Widespread inflammation is accompanied by metabolic disruptions. These include not only insulin resistance, type II diabetes, and fatty liver disease, but also atherosclerotic changes in blood vessels, heart disease, and stroke.5,6
Inflammatory changes in the brain and bone lead to neurodegenerative disorders and osteoporosis, respectively.7,8 At some point, DNA repair mechanisms and cell replication controls are lost, with a concomitant spike in cancer development.6,9
In short, fat tissue is perhaps the most powerful accelerator of aging.
Quercetin Prevents Obesity
The first step in protecting against obesity-related health dangers is to prevent diet-induced obesity in the first place.
A study published in early 2018 showed that quercetin could help prevent diet-induced obesity—even in the presence of a high-fat diet.
For the study, rats were fed either a normal diet, a high-fat diet, or a high-fat diet along with a quercetin-rich dietary supplement.10
After 8 weeks, rats in the groups fed high-fat diets gained weight compared with those on a normal diet. However, the quercetin-supplemented rats fed a high-fat diet gained 8.5% less weight by the end of the study, compared with those fed the high-fat diet alone.10
The prevention of weight gain was accompanied by impressive protections against internal fat accumulations. By the end of the study, compared to high-fat diet controls, quercetin-supplemented animals on high-fat diets had:
- 23% less total body fat,
- 23.8% lower serum triglyceride levels, and
- 22% less visceral (abdominal) fat.
Improvements at the Cellular Level
These macroscopic improvements in body weight, fat distribution, and lipid profile were accompanied by microscopic changes in the architecture of liver and fat cells.10
Healthy, lean animals have dense, well-organized liver cells lacking any droplets of free fat.
Rats fed a high-fat diet have loose, poorly-organized liver tissue riddled with droplets of free fat that won’t stay in cells.
Lean animals have compact, small fat cells, while rats fed a high-fat diet have enlarged, overfilled fat cells.10
These changes in the structure of the cell negatively impact health because a liver loaded with fat cells (fatty liver) is a highly inflammatory environment.11 This situation may lead to poor liver function, declining insulin sensitivity, and eventually to liver damage leading to cirrhosis, fibrosis, and liver failure.
Large, unhealthy fat cells elsewhere in the body only add to the inflammatory burden12—which adds to the risks of inflammation-driven diseases like heart attacks, strokes, cancer, and even osteoporosis.
This study found that when rats fed a high-fat diet were also fed a quercetin-rich supplement, the architecture of their liver and fat cells changed to closely resemble those of lean animals fed a normal diet, with few liver oil droplets and small, orderly fat cells.10
Overall, this study shows that quercetin helps reduce diet-induced weight gain while also protecting tissues from excessive, destructive fat inflammation.
But what we learn from this study is only a portion of the story. Still more exciting is the emerging picture of what quercetin can do to existing fat stores—activity that amounts to a detoxification of fat tissue.
The result is the promotion of health and deceleration of aging.
Quercetin’s Multi-Targeted Effects
Two animal studies published in the past several years have demonstrated that supplementing with quercetin contributes to significant reductions in body weight—while also protecting against the dangerous impact of diet-induced accumulation of fat.13,14
Together, these studies offer a comprehensive picture of quercetin’s ability to attack obesity on multiple levels.
Here are the four primary ways quercetin accomplishes these feats.
Quercetin Reduces Fat-Generated Inflammation
Animal studies show that supplementation with quercetin (when given in combination with resveratrol) works in two key ways to reduce obesity-induced inflammation.
First, quercetin precisely controls the genetic expression of pro-inflammatory signaling molecules (cytokines). In addition, this nutrient combination has been shown to produce significant reductions in the size of body-fat stores, to lower body weight, result in smaller fat- cell sizes, and reduce blood lipid levels.15
An even more striking finding is quercetin’s effect on the hypothalamus, the body’s central metabolic regulatory center.16
Obesity can activate the immune cells of the central nervous system, called microglia, producing destructive, localized inflammation, including in the hypothalamus. Inflammation in the hypothalamus has far-reaching consequences because of its intimate involvement in everything from core body temperature to basal metabolic rate to appetite and activity.
By activating microglia, obesity has been implicated in upsetting the ways the body manages its energy balance, as well as in metabolic complications like diabetes, and in neurodegenerative diseases.17-22
A recent animal study found that quercetin can reduce obesity-induced inflammation in the hypothalamus of obese mice. It accomplishes this by inducing an enzyme that protects brain tissues against oxidative stress that drives inflammation.16
By reducing fat-generated inflammation, quercetin combats a potent age-accelerator.15,23
Quercetin Upregulates AMPK
AMPK is one of the body’s central metabolic regulatory signaling enzymes and is found in every living cell. It is considered one of the body’s most powerful anti-aging tools.
When activated, AMPK enhances rates of energy extraction by burning fat, and accelerating cleanup of toxic debris that accumulates inside aging cells (autophagy).
Quercetin has been shown to activate AMPK.14,15 Doing so promotes a more youthful cell type in terms of activity and vulnerability to stress of all kinds.24-26
A study of rats fed a high-fat diet (which induced obesity) showed that quercetin stopped fat-induced suppression of AMPK. This freed the animals’ cells to revert to more youthful activity, while also reducing many inflammatory processes.15
Quercetin Promotes a Healthy Gut Microbiome
The gut microbiome is the community of millions of microorganisms that live in the intestinal tract. Obesity contributes to an imbalanced microbiome (called dysbiosis), a problem that is closely related to a wide range of human health issues, including diabetes and cardiovascular disease.27-29
Research suggests that obesity-related dysbiosis may produce “leaky gut,”30 a condition that
allows bacterial toxins to enter the
bloodstream, while promoting liver damage and excessive inflammation.
In a mouse study, treatment with quercetin restored balance to the gut microbiome and turned off dysbiosis-related inflammatory and stress responses.31
One dramatic consequence of this effect of quercetin is a reduction in the severity of obesity-induced, non-alcoholic fatty liver disease (NAFLD).31
NAFLD is a serious consequence of insulin resistance and can lead to non-alcoholic steatohepatitis, which is a precursor of liver cirrhosis and even liver cancer.32
Supplementing with quercetin achieves these gut-microbiome-related results by interacting with the many species that make up the gut microbiome. It stops the growth of bacteria that have pro-inflammatory and other harmful properties, while promoting the growth of bacteria known to protect the gut by producing mucous and anti-inflammatory compounds.23,33
In short, quercetin harnesses gut bacteria as allies in the fight against total-body impacts of obesity.
Quercetin Converts White Fat to Brown Fat
The bulk of fat tissue in adults is composed of white adipose tissue, or simply “white fat.”
This type of fat is what provides our energy supply between meals.34 Unfortunately, it is also the source of inflammation and other harmful metabolic changes associated with excessive fat stores.11,27
But infants (and many small mammals) have fat deposits that are made up of brown adipose tissue, or simply “brown fat.” Unlike the white variety, brown fat has the capability of converting energy stored as fat into heat.35,36
Research shows that mice with increased numbers of brown fat cells are lean and protected from obesity, compared with those dominated by white fat.37
We’re now learning that it’s possible to boost brown-fat-cell content in human adults by triggering the cellular switch from white to brown.34-41 The result is the conversion of stored fat into fat that is burned for energy and readily shed from the body.
It’s a discovery that is revolutionizing our approach to obesity—and quercetin could play a major role.
Animal studies have now demonstrated that quercetin—either alone or in combination with resveratrol—can convert white fat cells into those resembling brown fat cells.40,42,43
This “browning” process is a promising strategy for mitigating the impact of obesity.42
As an added benefit, quercetin-induced fat-browning increases the activity of PPAR-alpha, a gene regulator that promotes the expression of genes involved in burning fat and glucose.40
Summary
Obesity is a major threat to human health and longevity.
Excessive amounts of certain types of fat tissue generate inflammation that accelerates the aging process and leads to insulin resistance, diabetes, heart disease, cancer, osteoporosis, and even neurodegenerative disorders.
Quercetin has been shown to help protect against obesity itself, as well as its age-accelerating consequences.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
References
- Fontana L, Hu FB. Optimal body weight for health and longevity: bridging basic, clinical, and population research. Aging Cell. 2014 Jun;13(3):391-400.
- Available at: https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity. Accessed December 3, 2018.
- Pasarica M, Sereda OR, Redman LM, et al. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes. 2009 Mar;58(3):718-25.
- Leiherer A, Stoemmer K, Muendlein A, et al. Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes. Nutrients. 2016 May 12;8(5).
- Bonaccio M, Di Castelnuovo A, Pounis G, et al. A score of low-grade
inflammation and risk of mortality: prospective findings from the Moli-sani
study. Haemato
logica. 2016 Nov;101(11):1434-41. - Shimizu I, Yoshida Y, Suda M, et al. DNA damage response and metabolic disease. Cell Metab. 2014 Dec 2;20(6):967-77.
- Lacativa PG, Farias ML. Osteoporosis and inflammation. Arq Bras Endocrinol Metabol. 2010 Mar;54(2):123-32.
- Ginaldi L, Di Benedetto MC, De Martinis M. Osteoporosis, inflammation and ageing. Immun Ageing. 2005 Nov 4;2:14.
- Kawanishi S, Ohnishi S, Ma N, et al. Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis. Int J Mol Sci. 2017 Aug 19;18(8):1808.
- Ting Y, Chang WT, Shiau DK, et al. Antiobesity Efficacy of Quercetin-Rich Supplement on Diet-Induced Obese Rats: Effects on Body Composition, Serum Lipid Profile, and Gene Expression. J Agric Food Chem. 2018 Jan 10;66(1):70-80.
- Trayhurn P, Bing C, Wood IS. Adipose tissue and adipokines--energy regulation from the human perspective. J Nutr. 2006 Jul;136(7 Suppl):1935S-9S.
- Kuo FC, Huang YH, Lin FH, et al. Circulating Soluble IL-6 Receptor Concentration and Visceral Adipocyte Size Are Related to Insulin Resistance in Taiwanese Adults with Morbid Obesity. Metab Syndr Relat Disord. 2017 May;15(4):187-93.
- Jung CH, Cho I, Ahn J, et al. Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes. Phytother Res. 2013 Jan;27(1):139-43.
- Dong J, Zhang X, Zhang L, et al. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKalpha1/SIRT1. J Lipid Res. 2014 Mar;55(3):363-74.
- Zhao L, Cen F, Tian F, et al. Combination treatment with quercetin and resveratrol attenuates high fat diet-induced obesity and associated inflammation in rats via the AMPKalpha1/SIRT1 signaling pathway. Exp Ther Med. 2017 Dec;14(6):5942-8.
- Yang J, Kim CS, Tu TH, et al. Quercetin Protects Obesity-Induced Hypothalamic Inflammation by Reducing Microglia-Mediated Inflammatory Responses via HO-1 Induction. Nutrients. 2017 Jun 23;9(7).
- de Kloet AD, Pioquinto DJ, Nguyen D, et al. Obesity induces neuroinflammation mediated by altered expression of the renin-angiotensin system in mouse forebrain nuclei. Physiol Behav. 2014 Sep;136:31-8.
- Politis M, Pavese N, Tai YF, et al. Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum Brain Mapp. 2011 Feb;32(2):258-70.
- Rana I, Badoer E, Alahmadi E, et al. Microglia are selectively activated in endocrine and cardiovascular control centres in streptozotocin-induced diabetic rats. J Neuroendocrinol. 2014 Jul;26(7):413-25.
- Sugama S. Stress-induced microglial activation may facilitate the progression of neurodegenerative disorders. Med Hypotheses. 2009 Dec;73(6):1031-4.
- Valdearcos M, Douglass JD, Robblee MM, et al. Microglial Inflammatory Signaling Orchestrates the Hypothalamic Immune Response to Dietary Excess and Mediates Obesity Susceptibility. Cell Metab. 2017 Jul 5;26(1):185-97 e3.
- Valdearcos M, Robblee MM, Benjamin DI, et al. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep. 2014 Dec 24;9(6):2124-38.
- Zhao L, Zhang Q, Ma W, et al. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct. 2017 Dec 13;8(12):4644-56.
- Angin Y, Beauloye C, Horman S, et al. Regulation of Carbohydrate Metabolism, Lipid Metabolism, and Protein Metabolism by AMPK. EXS. 2016;107:23-43.
-
Gabryel B, Kost A, Kasprowska D, et al. AMP-activated protein kinase is
involved in induction of protective autophagy in
astrocytes exposed to oxygen-glucose deprivation. Cell Biol Int. 2014 Oct;38(10): 1086-97. - Li C, Yu L, Xue H, et al. Nuclear AMPK regulated CARM1 stabilization impacts autophagy in aged heart. Biochem Biophys Res Commun. 2017 Apr 29;486(2):398-405.
- Bleau C, Karelis AD, St-Pierre DH, et al. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes. Diabetes Metab Res Rev. 2015 Sep;31(6):545-61.
- Hartstra AV, Bouter KE, Backhed F, et al. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015 Jan;38(1):159-65.
- Miele L, Giorgio V, Alberelli MA, et al. Impact of Gut Microbiota on Obesity, Diabetes, and Cardiovascular Disease Risk. Curr Cardiol Rep. 2015 Dec;17(12):120.
- Nagpal R, Newman TM, Wang S, et al. Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet. J Diabetes Res. 2018;2018:3462092.
- Porras D, Nistal E, Martinez-Florez S, et al. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med. 2017 Jan;102:188-202.
- Caligiuri A, Gentilini A, Marra F. Molecular Pathogenesis of NASH. Int J Mol Sci. 2016 Sep 20;17(9):1575.
- Etxeberria U, Arias N, Boque N, et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J Nutr Biochem. 2015 Jun;26(6):651-60.
- Cinti S. UCP1 protein: The molecular hub of adipose organ plasticity. Biochimie. 2017 Mar;134:71-6.
- Schulz TJ, Huang TL, Tran TT, et al. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):143-8.
- Contreras GA, Lee YH, Mottillo EP, et al. Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab. 2014 Nov 1;307(9):E793-9.
- Elattar S, Satyanarayana A. Can Brown Fat Win the Battle Against White Fat? J Cell Physiol. 2015 Oct;230(10):2311-7.
- Nyman E, Bartesaghi S, Melin Rydfalk R, et al. Systems biology reveals uncoupling beyond UCP1 in human white fat-derived beige adipocytes. NPJ Syst Biol Appl. 2017;3:29.
- Zietak M, Chabowska-Kita A, Kozak LP. Brown fat thermogenesis: Stability of developmental programming and transient effects of temperature and gut microbiota in adults. Biochimie. 2017 Mar;134:93-8.
- Castrejon-Tellez V, Rodriguez-Perez JM, Perez-Torres I, et al. The Effect of Resveratrol and Quercetin Treatment on PPAR Mediated Uncoupling Protein (UCP-) 1, 2, and 3 Expression in Visceral White Adipose Tissue from Metabolic Syndrome Rats. Int J Mol Sci. 2016 Jul 5;17(7).
- Langin D. Recruitment of brown fat and conversion of white into brown adipocytes: strategies to fight the metabolic complications of obesity? Biochim Biophys Acta. 2010 Mar;1801(3):372-6.
- Lee SG, Parks JS, Kang HW. Quercetin, a functional compound of onion peel, remodels white adipocytes to brown-like adipocytes. J Nutr Biochem. 2017 Apr;42:62-71.
- Arias N, Pico C, Teresa Macarulla M, et al. A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet. Obesity (Silver Spring). 2017 Jan;25(1):111-21.