J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website http://www.jofem.org

Review

Volume 2, Number 4-5, October 2012, pages 155-165

Metabolic Syndrome: A Multifaceted Disease of Affluence

Figure 1. Relationships between high-energy (high-lipid) diet and inflammation and its main consequences, diabetes and obesity.

Figure 2. Consequences of white adipose tissue (WAT) defence against excess energy and its relationship with inflammation and hypertension.

Figure 3. Chain of events caused by hyperlipidic high-energy diets to the last energy sink, white adipose tissue (WAT), causing generalized inflammation, and the basis of the metabolic syndrome.

**Table 1.** Main Pathologic Traits Associated With the Metabolic Syndrome
Insulin resistance	Decreased sensitivity to glucose/Low peripheral tissue glucose uptake/Type 2 diabetes/Dementia/Alzheimer disease
Hyperlipidemia/dyslipoproteinemia	Small, dense LDLs/Hypercholesterolemia and low HDL cholesterol/Hypertriacylglycerolemia/High ApoB/Oxidized lipoproteins
Hepatic steatosis and hepatomegalia, Altered hepatic function	hyperbilirubinemia/Increased enzyme leakage/Altered antioxidant mechanisms/Altered xenobiotic metabolism
Hyperuricemia/gout	Inflammatory arthritis
White adipose tissue inflammation	Obesity/visceral or upper body obesity/Adipocyte hyperplasia and proliferation/High proportion of nonadipocyte cells/massive macrophage infiltration/Altered blood flow/Hypoxia/High leptin/leptin resistance/Low adiponectin/High resistin Low interleukin-6/increased adipokine signaling
Altered immune response	Asthma, psoriasis/Other autoimmune diseases
Increased oxidative damage	Increased effects of free radicals, superoxide, peroxynitrite, etc./Increased synthesis and disposal of NO·/Increased nitrite and nitrate excretion
Altered composition of the microbiota	Altered immune system control of the biota/presence of nitrate and nitrite/Increased LPS levels/interaction with the biota
Acanthosis nigricans
Sleep apnea
Arterial hypertension	Increased peripheral blood flow resistance/Atherosclerosis/increased vascular microdamage and enhanced plaque formation/Altered rheological behavior of red blood cells/nondeformability of red blood cells
Increased cardiovascular risk	Atrial fibrillation/Altered blood coagulation/Pulmonary resistance/respiratory insufficiency/Heart insufficiency/Higher incidence of ictus
Altered hypothalamic-pituitary-adrenals axis function	Hypercortisolism/Cushing-like states/Disappearance of daily rhythms/Depression, altered thymic states/Altered gonadotropin secretion, infertility
Decreased/altered sex hormone metabolism and function	Polycystic ovary syndrome (?)/Hypoandrogenism/Decreased dehydroepiandrosterone/Decreased estrogen protection
Altered nervous system functions	Decreased cognoscitive abilities/Higher incidence of psychiatric alterations/Higher autonomic nervous system activity/Peripheral nerve damage
Eating disorders:	Binge eating (obesity type)/Orthorexia, anorexia nervosa (secondary)
Increased incidence of some types of cancer	Colon, endometrial, renal cell, gallbladder, and upper digestive tracts carcinomas (largely associated with obesity, diet, and estrogen)

Table 1. Main Pathologic Traits Associated With the Metabolic Syndrome

Insulin resistance

Decreased sensitivity to glucose/Low peripheral tissue glucose uptake/Type 2 diabetes/Dementia/Alzheimer disease

Hyperlipidemia/dyslipoproteinemia

Small, dense LDLs/Hypercholesterolemia and low HDL cholesterol/Hypertriacylglycerolemia/High ApoB/Oxidized lipoproteins

Hepatic steatosis and hepatomegalia, Altered hepatic function

hyperbilirubinemia/Increased enzyme leakage/Altered antioxidant mechanisms/Altered xenobiotic metabolism

Hyperuricemia/gout

Inflammatory arthritis

White adipose tissue inflammation

Obesity/visceral or upper body obesity/Adipocyte hyperplasia and proliferation/High proportion of nonadipocyte cells/massive macrophage infiltration/Altered blood flow/Hypoxia/High leptin/leptin resistance/Low adiponectin/High resistin
Low interleukin-6/increased adipokine signaling

Altered immune response

Asthma, psoriasis/Other autoimmune diseases

Increased oxidative damage

Increased effects of free radicals, superoxide, peroxynitrite, etc./Increased synthesis and disposal of NO·/Increased nitrite and nitrate excretion

Altered composition of the microbiota

Altered immune system control of the biota/presence of nitrate and nitrite/Increased LPS levels/interaction with the biota

Acanthosis nigricans

Sleep apnea

Arterial hypertension

Increased peripheral blood flow resistance/Atherosclerosis/increased vascular microdamage and enhanced plaque formation/Altered rheological behavior of red blood cells/nondeformability of red blood cells

Increased cardiovascular risk

Atrial fibrillation/Altered blood coagulation/Pulmonary resistance/respiratory insufficiency/Heart insufficiency/Higher incidence of ictus

Altered hypothalamic-pituitary-adrenals axis function

Hypercortisolism/Cushing-like states/Disappearance of daily rhythms/Depression, altered thymic states/Altered gonadotropin secretion, infertility

Decreased/altered sex hormone metabolism and function

Polycystic ovary syndrome (?)/Hypoandrogenism/Decreased dehydroepiandrosterone/Decreased estrogen protection

Altered nervous system functions

Decreased cognoscitive abilities/Higher incidence of psychiatric alterations/Higher autonomic nervous system activity/Peripheral nerve damage

Eating disorders:

Binge eating (obesity type)/Orthorexia, anorexia nervosa (secondary)

Increased incidence of some types of cancer

Colon, endometrial, renal cell, gallbladder, and upper digestive tracts carcinomas (largely associated with obesity, diet, and estrogen)