Recent Progress in Metabolic Syndrome Research and Therapeutics

Kao, Tsair; Huang, Chin‐Chou

doi:10.3390/ijms22136862

Cited by 23 publications

(20 citation statements)

References 112 publications

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“…The metabolic syndrome that may include insulin resistance, NAFLD, chronic low-level inflammation, as well as other serious co-morbidities [ 1 ]. Precipitated mainly by obesity, the metabolic syndrome may eventually lead to type 2 diabetes (T2D) [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist

Phillips

Lantier

Engman

et al. 2022

Cardiovasc Diabetol

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Background Liver pathology (LP) characteristic of non-alcoholic fatty acid disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is a prevalent co-morbidity of type 2 diabetes (T2D). Accumulating evidence indicates that neutrophils driving insulin resistance (IR), including hepatic IR, precipitate T2D-associated NAFLD/NASH. We hypothesized that targeting neutrophil accumulation into insulin-sensitive tissues in mice using a CXCR2 antagonist under T2D-precipitating high fat diet (HFD) could improve insulin sensitivity and prevent the progression towards liver pathology reminiscent of NAFLD/NASH. Methods Mice were age-matched and on standard rodent chow prior to 1:1 randomization into control and HFD formulated with the CXCR2 antagonist AZD5069 or with biologically inactive substitute. They were monitored for metabolic changes including insulin sensitivity using the hyperinsulinemic-euglycemic clamp and hepatic histopathologic evaluation in H&E-stained sections as well as via immunofluorescence microscopy of liver sections for leukocyte markers, collagen 1A1 formation, α-smooth muscle actin (SMA), and galectin-3 expression, for 16 weeks. Statistical tests used to determine significant differences among study groups and outcomes include Student’s t-test, one-way ANOVA, repeated measures two-way ANOVA, and Fisher’s exact test, depending on the analytical question. Results Compared to mice on HFD, mice in the AZD5069-formulated HFD exhibited improved insulin sensitivity, a modest reduction in weight gain, and a significant improvement in LP and markers related to NAFLD/NASH. Mice in the AZD5069-formulated HFD also exhibited reduced neutrophil accumulation into the liver at the end of the 16 week study period. Conclusions These results show, for the first time, the effectiveness of a selective CXCR2 antagonist to improve insulin sensitivity, concomitantly preventing the progression towards LP characteristic of NAFLD/NASH. This represents a novel approach to target IR and developing LP under T2D-susceptible conditions using a single agent. Furthermore, our data extend the growing evidence in support of neutrophils as a leukocyte population that imprints and maintains a chronic inflammatory state in the progression of dysregulated metabolism in liver-specific co-morbid conditions.

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Section: Introductionmentioning

confidence: 99%

Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist

Phillips

Lantier

Engman

et al. 2022

Cardiovasc Diabetol

View full text Add to dashboard Cite

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“…Metabolic syndrome remains the most common non-communicable disease that is characterized by central obesity, insulin resistance, hyperlipidaemia, and hypertension ( Bishehsari et al, 2020 ). MetS increases the risk of developing several chronic diseases, including T2DM, NAFLD, cardiovascular diseases, and cancer ( Chen et al, 2021b ; Kao and Huang, 2021 ). The contributors of MetS include genetic factors, and lifestyle, such as dietary over-consumption of HFD ( Wutthi-In et al, 2020 ).…”

Section: Metabolic Syndromementioning

confidence: 99%

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

et al. 2022

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Unhealthy diet, in particular high-fat diet (HFD) intake, can cause the development of several metabolic disorders, including obesity, hyperlipidemia, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS). These popular metabolic diseases reduce the quality of life, and induce premature death worldwide. Evidence is accumulating that the gut microbiota is inextricably associated with HFD-induced metabolic disorders, and dietary intervention of gut microbiota is an effective therapeutic strategy for these metabolic dysfunctions. Polysaccharides are polymeric carbohydrate macromolecules and sources of fermentable dietary fiber that exhibit biological activities in the prevention and treatment of HFD-induced metabolic diseases. Of note, natural polysaccharides are among the most potent modulators of the gut microbiota composition. However, the prebiotics-like effects of polysaccharides in treating HFD-induced metabolic diseases remain elusive. In this review, we introduce the critical role of gut microbiota human health and HFD-induced metabolic disorders. Importantly, we review current knowledge about the role of natural polysaccharides in improving HFD-induced metabolic diseases by regulating gut microbiota.

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“…Clinically, the impacts of inflammatory status induced by gut dysbiosis have been displayed in a wide spectrum of cardiovascular disease. Our previous review summarised the correlation between gut microbiota and inflammation in patients with metabolic syndrome [ 68 ]. Luedde et al observed a significantly lower diversity index in 20 individuals with heart failure secondary to ischaemic or dilated cardiomyopathy, which was marked by the depletion of Coriobacteriaceae , Erysipelotrichaceae , and Ruminococcaceae [ 69 ].…”

Section: The Role Of Gut Microbiotamentioning

confidence: 99%

Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases

Kao

Huang

2022

IJMS

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Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1β and −6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.

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Recent Progress in Metabolic Syndrome Research and Therapeutics

Cited by 23 publications

References 112 publications

Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist

Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases

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