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Fructose-induced Inflammation and Increased Cortisol: A New Mechanism for How Sugar Induces Visceral Adiposity

Published on Dec 1, 2017in Progress in Cardiovascular Diseases 6.16
· DOI :10.1016/j.pcad.2017.12.001
James J. DiNicolantonio24
Estimated H-index: 24
,
Varshil Mehta8
Estimated H-index: 8
(M.G.M. Medical College)
+ 1 AuthorsJames H. O'Keefe52
Estimated H-index: 52
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Abstract
Abstract Traditionally, the leading hypothesis regarding the development of obesity involves caloric imbalance, whereby the amount of calories consumed exceeds the amount of calories burned which causes obesity. Another hypothesis for why we get fat has surfaced in the last decade which is the idea that the overconsumption of added sugars and refined carbohydrates induce insulin resistance and high insulin levels causing obesity. While insulin is a fat-storing hormone, this hypothesis does not explain visceral adiposity, or why certain people are found to have fat stored in and around their organs. We propose a new mechanism for body fattening, particular visceral adiposity. This hypothesis involves the overconsumption of fructose, which leads to inflammation in all cells that metabolize it rapidly. When fructose is metabolized in subcutaneous adipocytes, the subsequent inflammation leads to an increase in intracellular cortisol in order to help squelch the inflammation. Unfortunately, the increase in intracellular cortisol leads to an increased flux of fatty acids out of the subcutaneous adipocytes allowing more substrate for fat storage into visceral fat tissue. Moreover fructose-induced inflammation in the liver also leads to increased intracellular cortisol via an upregulation of 11-B hydroxysteroid dehydrogenase type 1 causing increased fat storage in the liver (i.e., fatty liver). In essence, the fructose-induced inflammatory cortisol response causes "thin on the outside, fat on the inside" (TOFI). Furthermore, fructose in the brain, either from fructose uptake via the blood brain barrier or endogenous formation from glucose via the polyol pathway stimulates an increased release of cortisol causing hepatic gluconeogenesis leading to overall insulin resistance and further body fattening. This review paper will discuss in detail the hypothesis that fructose-induced inflammation and cortisol activation causes visceral adiposity.
  • References (113)
  • Citations (3)
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References113
Newest
Published on Mar 1, 2016in Progress in Cardiovascular Diseases 6.16
Evan O’Keefe3
Estimated H-index: 3
(Emory University),
James J. DiNicolantonio24
Estimated H-index: 24
+ 2 AuthorsCarl J. Lavie82
Estimated H-index: 82
(UQ: University of Queensland)
Abstract Within the next 15 years, India is projected to overtake China as the world's most populous nation. Due to the rapid pace of urbanization and modernization fueling population growth, in conjunction with a genetic predisposition to insulin resistance, India is suffering a rising epidemic of non-communicable diseases (NCDs), including coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), and stroke. In addition to the genetic predisposition, major negative lifestyle factors are ...
24 Citations Source Cite
Published on Mar 1, 2016in Progress in Cardiovascular Diseases 6.16
James J. DiNicolantonio24
Estimated H-index: 24
,
Sean C. Lucan18
Estimated H-index: 18
,
James H. O'Keefe52
Estimated H-index: 52
Dietary guidelines continue to recommend restricting intake of saturated fats. This recommendation follows largely from the observation that saturated fats can raise levels of total serum cholesterol (TC), thereby putatively increasing the risk of atherosclerotic coronary heart disease (CHD). However, TC is only modestly associated with CHD, and more important than the total level of cholesterol in the blood may be the number and size of low-density lipoprotein (LDL) particles that contain it. A...
59 Citations Source Cite
Published on Jul 1, 2015
James J. DiNicolantonio24
Estimated H-index: 24
,
James H. O'Keefe52
Estimated H-index: 52
(UMKC: University of Missouri–Kansas City),
Sean C. Lucan18
Estimated H-index: 18
4 Citations Source Cite
Published on Mar 1, 2015
James J. DiNicolantonio24
Estimated H-index: 24
,
James H. O'Keefe52
Estimated H-index: 52
,
Sean C. Lucan18
Estimated H-index: 18
(Albert Einstein College of Medicine)
Abstract Data from animal experiments and human studies implicate added sugars (eg, sucrose and high-fructose corn syrup) in the development of diabetes mellitus and related metabolic derangements that raise cardiovascular (CV) risk. Added fructose in particular (eg, as a constituent of added sucrose or as the main component of high-fructose sweeteners) may pose the greatest problem for incident diabetes, diabetes-related metabolic abnormalities, and CV risk. Conversely, whole foods that contain...
55 Citations Source Cite
Published on Sep 1, 2014in European Journal of Nutrition 4.45
Ana Vasiljević7
Estimated H-index: 7
(University of Belgrade),
Biljana Bursać7
Estimated H-index: 7
(University of Belgrade)
+ 4 AuthorsNataša Veličković9
Estimated H-index: 9
(University of Belgrade)
Purpose High fructose consumption provokes metabolic perturbations that result in chronic low-grade inflammation and insulin resistance. Glucocorticoids, potent anti-inflammatory hormones, have important role in pathogenesis of diet-induced metabolic disturbances. The aim of this study was to examine the link between glucocorticoid metabolism and inflammation in the liver of fructose-fed rats.
20 Citations Source Cite
Published on Dec 31, 2013in PLOS Medicine
Maira Bes-Rastrollo DPharm39
Estimated H-index: 39
(University of Navarra),
Matthias B. Schulze67
Estimated H-index: 67
+ 1 AuthorsMiguel A. Martínez-González85
Estimated H-index: 85
(University of Navarra)
Background: Industry sponsors’ financial interests might bias the conclusions of scientific research. We examined whether financial industry funding or the disclosure of potential conflicts of interest influenced the results of published systematic reviews (SRs) conducted in the field of sugar-sweetened beverages (SSBs) and weight gain or obesity. Methods and Findings: We conducted a search of the PubMed, Cochrane Library, and Scopus databases to identify published SRs from the inception of the ...
129 Citations Source Cite
Published on Mar 1, 2013in Advances in Nutrition 7.24
John S. White1
Estimated H-index: 1
The field of sugar metabolism, and fructose metabolism in particular, has experienced a resurgence of interest in the past decade. The “fructose hypothesis” alleges that the fructose component common to all major caloric sweeteners (sucrose, high-fructose corn syrup, honey, and fruit juice concentrates) plays a unique and causative role in the increasing rates of cardiovascular disease, hypertension, diabetes, cancer, and nonalcoholic fatty liver disease. This review challenges the fructose hypo...
83 Citations Source Cite
Published on Jan 2, 2013in JAMA 51.27
Kathleen A. Page14
Estimated H-index: 14
,
Owen Chan14
Estimated H-index: 14
+ 8 AuthorsR. Todd Constable81
Estimated H-index: 81
Importance Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety. Objective To study neurophysiological factors that might underlie associations bet...
200 Citations Source Cite
Published on Jan 1, 2013in Physiological Reviews 24.25
André Tchernof48
Estimated H-index: 48
,
Jean-Pierre Després110
Estimated H-index: 110
Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-r...
791 Citations Source Cite
Published on Jan 1, 2013in Global Public Health 1.94
Michael I. Goran85
Estimated H-index: 85
(SC: University of Southern California),
Stanley J. Ulijaszek25
Estimated H-index: 25
(University of Oxford),
Emily E. Ventura22
Estimated H-index: 22
(SC: University of Southern California)
Abstract The overall aim of this study was to evaluate, from a global and ecological perspective, the relationships between availability of high fructose corn syrup (HFCS) and prevalence of type 2 diabetes. Using published resources, country-level estimates (n =43 countries) were obtained for: total sugar, HFCS and total calorie availability, obesity, two separate prevalence estimates for diabetes, prevalence estimate for impaired glucose tolerance and fasting plasma glucose. Pearson's correlati...
105 Citations Source Cite
Cited By3
Newest
Published on Jul 1, 2019in Progress in Cardiovascular Diseases 6.16
Carl J. Lavie82
Estimated H-index: 82
(UQ: University of Queensland)
Source Cite
Published on Jan 1, 2019in International Journal of Molecular Sciences 4.18
Adrián Hernández-Díazcouder , Rodrigo Romero-Nava3
Estimated H-index: 3
+ 2 AuthorsFausto Sánchez-Muñoz3
Estimated H-index: 3
In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues. Several tissues including adipose tissue express the main fructose transporter GLUT5. In vivo, chronic fruct...
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Published on Mar 26, 2019in Frontiers in Neuroscience 3.65
Helen M. Melo7
Estimated H-index: 7
,
Luís Eduardo Santos8
Estimated H-index: 8
,
Sergio T. Ferreira46
Estimated H-index: 46
Western societies experienced drastic changes in eating habits during the past century. The modern nutritional profile, typically rich in saturated fats and refined sugars, is recognized as a major contributing factor, along with reduced physical activity, to the current epidemics of metabolic disorders, notably obesity and diabetes. Alongside these conditions, recent years have witnessed a gradual and significant increase in prevalence of brain diseases, particularly mood disorders. While subst...
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Published on Feb 1, 2019in Molecular and Cellular Endocrinology 3.69
Thereza Cristina Lonzetti Bargut9
Estimated H-index: 9
(Federal Fluminense University),
Thereza Cristina Lonzetti Bargut1
Estimated H-index: 1
(Federal Fluminense University)
+ 2 AuthorsMandarim de Lacerda32
Estimated H-index: 32
(UERJ: Rio de Janeiro State University)
Abstract The role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in browning and thermogenesis has not been fully elucidated. Thus, we meant to evaluate the effect of EPA and DHA, administered alone or combined, with the activation of browning markers in subcutaneous white adipose tissue (sWAT), and thermogenic markers in brown adipose tissue (BAT). C57BL/6 adult male mice received a control diet or a high-fructose diet (HFru) for eight weeks, but after the first three weeks, HFru...
1 Citations Source Cite
Published on Jun 13, 2018in BMJ 27.60
David S. Ludwig66
Estimated H-index: 66
(Harvard University),
Frank B. Hu202
Estimated H-index: 202
(Harvard University)
+ 1 AuthorsJennie Brand-Miller50
Estimated H-index: 50
(USYD: University of Sydney)
David S Ludwig and colleagues examine the links between different types of carbohydrates and health
18 Citations Source Cite