Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes

Reddy, P Balasundar; Lent-Schochet, Daniella; Ramakrishnan, Neeraj; McLaughlin, Matthew; Jialal, Ishwarlal

doi:10.1016/j.cca.2019.06.019

Cited by 218 publications

(170 citation statements)

References 79 publications

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“…High circulating acute phase inflammatory markers, i.e., C-reactive protein and fibrinogen have been linked to chronic inflammatory diseases such as MetS, diabetes, obesity, and CVD [50][51][52]. [53] suggesting that vitamin D is an anti-inflammatory agent [54].…”

Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Concentration ≥75 nmol/L Is Related to Decreased Cardiometabolic and Inflammatory Biomarkers, Metabolic Syndrome, and Diabetes; and Increased Cardiorespiratory Fitness in US Adults

2020

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A serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration of ≥75 nmol/L is recommended for optimal health. We investigated the relationship between serum 25(OH)D and metabolic syndrome (MetS), diabetes, cardiometabolic biomarkers, and cardiorespiratory fitness (CRF) in US adults using clinical cut points recommended by health organizations. Data from USA’s National Health and Nutrition Examination Surveys were used. Prevalences and likelihood of having MetS and diabetes according to clinical cut points for serum 25(OH)D (<30 nmol/L, 30-<50 nmol/L, 50-<75 nmo/L, and ≥75 nmol/L) were determined with multivariate logistic regression. Relations between serum 25(OH)D and various cardiometabolic biomarkers, CRF, MetS, and diabetes were tested using multivariable adjusted regression. Prevalence of MetS and diabetes were significantly lower in individuals with serum 25(OH)D ≥75 nmol/L (MetS, 21.6%; diabetes, 4.1%) compared to those with 25(OH)D <30 nmol/L (MetS, 45.5%; diabetes, 11.6%) (p < 0.0001). Individuals with serum 25(OH)D ≥75 nmol/L had significantly lower waist circumference (p < 0.0001), C-reactive protein (p = 0.003), glycated hemoglobin (p < 0.0002), fasting triglycerides (p < 0.0001), total homocysteine (p < 0.0001), and insulin resistance (p = 0.0001) and had significantly higher HDL-cholesterol (p < 0.0001) and maximal oxygen uptake (marker for CRF) (p< 0.0009) compared to those with 25(OH)D <30 nmol/L. In conclusion, serum 25(OH)D ≥75 nmol/L is associated with positive indicators related to cardiometabolic diseases in US adults.

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Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Concentration ≥75 nmol/L Is Related to Decreased Cardiometabolic and Inflammatory Biomarkers, Metabolic Syndrome, and Diabetes; and Increased Cardiorespiratory Fitness in US Adults

2020

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“…Since MS is also recognized as an inflammatory disorder [42], we checked several systemic inflammation markers in the serum. CRP (C-reactive protein), produced by the liver in response to inflammation, was found elevated in mice on HFD and was effectively reduced to a similar level as mice on CD by both low-dose and high dose of L-arabinose treatment; serum TNF-α (tumor necrosis factor alpha) level alterations exhibited similar pattern to serum CRP; serum IL-6 (interleukin 6) was also elevated in mice on HFD compared to mice on CD but was not altered by either low-dose or high dose of L-arabinose treatment ( Figure 4F).…”

Section: L-arabinose Effectively Alleviates Liver Steatosis As Well Amentioning

confidence: 99%

L-Arabinose Elicits Gut-Derived Hydrogen Production and Ameliorates Metabolic Syndrome in C57BL/6J Mice on High-Fat-Diet

et al. 2019

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Obesity and metabolic syndrome (MS) associated with excess calorie intake has become a great public health concern worldwide. L-arabinose, a naturally occurring plant pentose, has a promising future as a novel food ingredient with benefits in MS; yet the mechanisms remain to be further elucidated. Gut microbiota is recently recognized to play key roles in MS. Molecular hydrogen, an emerging medical gas with reported benefits in MS, can be produced and utilized by gut microbes. Here we show oral L-arabinose elicited immediate and robust release of hydrogen in mice in a dose-and-time-dependent manner while alleviating high-fat-diet (HFD) induced MS including increased body weight especially fat weight, impaired insulin sensitivity, liver steatosis, dyslipidemia and elevated inflammatory cytokines. Moreover, L-arabinose modulated gene-expressions involved in lipid metabolism and mitochondrial function in key metabolic tissues. Antibiotics treatment abolished L-arabinose-elicited hydrogen production independent of diet type, confirming gut microbes as the source of hydrogen. q-PCR of fecal 16S rDNA revealed modulation of relative abundances of hydrogen-producing and hydrogen-consuming gut microbes as well as probiotics by HFD and L-arabinose. Our data uncovered modulating gut microbiota and hydrogen yield, expression of genes governing lipid metabolism and mitochondrial function in metabolic tissues is underlying L-arabinose's benefits in MS.Nutrients 2019, 11, 3054 2 of 29 non-caloric sugars have become one of the rising stars among nutraceuticals with great potential in anti-MS application with reported benefits in both animal experiments and human studies.L-arabinose, a naturally occurring constituent of plant polysaccharides, usually extracted from vegetable gum, corn straw or beet, has gained considerable attention for its potential in anti-MS application recently. L-arabinose administration for 6 weeks reduces body weight, blood pressure, blood glucose, triglycerides, total cholesterol, serum insulin, serum TNF-α and serum leptin; and increases hepatic CPT1 and PDK4 mRNA level while decreases hepatic ACCα mRNA level in high-carbohydrate-high-fat-diet induced MS rats [1]. Polysaccharide from corn silk containing L-arabinose showed hypoglycemic and hypolipidemic effects on diabetic mice induced by high-fat-diet (HFD) and streptozotocin injection [2]. One mechanism underlying L-arabinose's benefits in MS has been demonstrated as directly inhibiting intestinal sucrase activity both in vitro and in human [3], which explains why L-arabinose effectively lower blood glucose and insulin level with ingestion of high-sucrose food or beverages but is unable to account for L-arabinose's benefits in MS in general. Therefore, more studies are urgently called to illuminate the mechanisms underlying L-arabinose's effects in HFD models, considering fat being a major source of energy intake in reality.Gut microbiota has been recognized to play a pathogenic role in the development of MS in both humans and animal models in the last...

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“…It is evident that monocytes isolated from obese humans with diabetes display an inflammatory phenotype and secrete higher levels of pro-inflammatory mediators such as IL-6, MCP-1, and IL-1β leading in metabolic dysfunction (29). Metabolic dysfunction is implicated in a wide-ranging effect on the immune cells, inflammation and lipid metabolism associated with adipocytes (30). TNF-α activates the plasma membrane nSMase2 that hydrolyzes sphingomyelin to ceramide results its accumulation within the cell (9).…”

Section: Discussionmentioning

confidence: 99%

Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α

Al-Rashed

Ahmad

Thomas

et al. 2020

Preprint

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Obesity is associated with elevated levels of TNF-α and proinflammatory CD11c monocytes /macrophages. TNF-α mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since neutral sphingomyelinase 2 (nSMase2; product of the sphingomyelin phosphodiesterase 3 gene, SMPD3) is a key enzyme for ceramide production involved in inflammation, we investigated whether nSMase2 contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-α. In this study, we demonstrate that the disruption of nSMase activity in monocytes/macrophages either by chemical inhibitor GW4869 or small interfering RNA (siRNA) against SMPD3 results in defects in the TNF-α mediated expression of CD11c. Furthermore, blockage of nSMase in monocytes/macrophages inhibited the secretion of inflammatory mediators IL-1b and MCP-1. In contrast, inhibition of acid SMase (aSMase) activity did not attenuate CD11c expression or secretion of IL-1b and MCP-1. TNF-α-induced phosphorylation of JNK, p38 and NF-κB was also attenuated by the inhibition of nSMase2. Moreover, NF-kB/AP-1 activity was blocked by the inhibition of nSMase2. SMPD3 was elevated in PBMCs from obese individuals and positively corelated with TNF-α gene expression. These findings indicate that nSMase2 acts, at least in part, as a master switch in the TNF-α mediated inflammatory responses in monocytes/macrophages.

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Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes

Cited by 218 publications

References 79 publications

Serum Vitamin D Concentration ≥75 nmol/L Is Related to Decreased Cardiometabolic and Inflammatory Biomarkers, Metabolic Syndrome, and Diabetes; and Increased Cardiorespiratory Fitness in US Adults

Serum Vitamin D Concentration ≥75 nmol/L Is Related to Decreased Cardiometabolic and Inflammatory Biomarkers, Metabolic Syndrome, and Diabetes; and Increased Cardiorespiratory Fitness in US Adults

L-Arabinose Elicits Gut-Derived Hydrogen Production and Ameliorates Metabolic Syndrome in C57BL/6J Mice on High-Fat-Diet

Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α

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