Citral, a valuable aid against metabolic inflammation?

The combination of obesity and type 2 diabetes is a serious health problem, which is projected to afflict 300 million people worldwide by 2020. Both clinical and translational laboratory studies have demonstrated that chronic inflammation is associated with obesity and obesity-related conditions such as insulin resistance. However, the precise etiopathogenetic mechanisms linking obesity to diabetes remain to be elucidated, and the pathways that mediate this phenomenon are not fully characterized. One of the most recently identified signaling pathways, whose activation seems to affect many metabolic disorders, is the “inflammasome,” a multiprotein complex composed of NLRP3 (nucleotide-binding domain and leucine-rich repeat protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), and procaspase-1. NLRP3 inflammasome activation leads to the processing and secretion of the proinflammatory cytokines interleukin- (IL-) 1βand IL-18. The goal of this paper is to review new insights on the effects of the NLRP3 inflammasome activation in the complex mechanisms of crosstalk between different organs, for a better understanding of the role of chronic inflammation in metabolic disease pathogenesis. We will provide here a perspective on the current research on NLRP3 inflammasome, which may represent an innovative therapeutic target to reverse the detrimental metabolic consequences of the metabolic inflammation.

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Inflammation and metabolism: the role of adiposity in sarcopenic obesity

Proceedings of The Nutrition Society ◽

10.1017/s0029665120007119 ◽

2020 ◽

Vol 79 (4) ◽

pp. 435-447

Author(s):

G. M. Lynch ◽

C. H. Murphy ◽

E. de Marco Castro ◽

H. M. Roche

Keyword(s):

Nutritional Status ◽

Sarcopenic Obesity ◽

Obesity Risk ◽

Dietary Interventions ◽

Double Burden ◽

Metabolic Inflammation ◽

Fat Composition ◽

Dietary Components ◽

Potential Impact

Sarcopenic obesity is characterised by the double burden of diminished skeletal muscle mass and the presence of excess adiposity. From a mechanistic perspective, both obesity and sarcopenia are associated with sub-acute, chronic pro-inflammatory states that impede metabolic processes, disrupting adipose and skeletal functionality, which may potentiate disease. Recent evidence suggests that there is an important cross-talk between metabolism and inflammation, which has shifted focus upon metabolic-inflammation as a key emerging biological interaction. Dietary intake, physical activity and nutritional status are important environmental factors that may modulate metabolic-inflammation. This paradigm will be discussed within the context of sarcopenic obesity risk. There is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation in sarcopenic obesity. Research suggests that there may be scope for the modulation of sarcopenic obesity with alterations in diet. The potential impact of increasing protein consumption and reconfiguration of dietary fat composition in human dietary interventions are evaluated. This review will explore emerging data with respect to if and how different dietary components may modulate metabolic-inflammation, particularly with respect to adiposity, within the context of sarcopenic obesity.

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Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation

Cellular Physiology and Biochemistry ◽

10.1159/000495487 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1051-1068 ◽

Cited By ~ 7

Author(s):

Jèssica Latorre ◽

José M. Moreno-Navarrete ◽

Mónica Sabater ◽

Maria Buxo ◽

José I. Rodriguez-Hermosa ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Inflammation ◽

Fat Depots ◽

Acute Surgery ◽

Obese Subjects ◽

Anti Inflammatory ◽

The Impact

Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.

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Metabolic inflammation: Connecting obesity and insulin resistance

Annals of Medicine ◽

10.3109/07853890.2012.705015 ◽

2012 ◽

Vol 45 (3) ◽

pp. 242-253 ◽

Cited By ~ 90

Author(s):

Nassim Dali-Youcef ◽

Mustapha Mecili ◽

Roméo Ricci ◽

Emmanuel Andrès

Keyword(s):

Insulin Resistance ◽

Metabolic Inflammation

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Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

Frontiers in Nutrition ◽

10.3389/fnut.2021.663838 ◽

2021 ◽

Vol 8 ◽

Author(s):

Domenico Sergi ◽

Natalie Luscombe-Marsh ◽

Nenad Naumovski ◽

Mahinda Abeywardena ◽

Nathan O'Callaghan

Keyword(s):

Insulin Resistance ◽

Membrane Potential ◽

Electron Transport ◽

Mitochondrial Membrane Potential ◽

Electron Transport Chain ◽

Mitochondrial Membrane ◽

Chain Complex ◽

Mitochondrial Fragmentation ◽

Metabolic Inflammation ◽

Transport Chain

The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 μM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.

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Pleiotropic Associations of RARRES2 Gene Variants and Circulating Chemerin Levels: Potential Roles of Chemerin Involved in the Metabolic and Inflammation-Related Diseases

Mediators of Inflammation ◽

10.1155/2018/4670521 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Leay-Kiaw Er ◽

Semon Wu ◽

Lung-An Hsu ◽

Ming-Sheng Teng ◽

Yu-Ching Sun ◽

...

Keyword(s):

Retinoic Acid Receptor ◽

Inflammatory Marker ◽

Density Lipoprotein ◽

Stepwise Logistic Regression ◽

Gene Variants ◽

Nucleotide Polymorphisms ◽

Lipocalin 2 ◽

Stepwise Logistic Regression Analysis ◽

Metabolic Inflammation ◽

Metabolic Phenotypes

Chemerin, an adipokine and inflammatory mediator, is associated with metabolic, inflammation- and immune-mediated diseases. The genetic, clinical, and biomarker correlates of circulating chemerin levels have not been completely elucidated. We analyzed the determinants and correlates of retinoic acid receptor responder 2 (RARRES2; encoding chemerin) gene variants and chemerin levels in the Taiwanese population. In total, 612 individuals were recruited. Clinical and metabolic phenotypes, 13 inflammatory markers, 5 adipokines, and 6 single-nucleotide polymorphisms (SNPs) covering the RARRES2 region were analyzed. High chemerin levels and chemerin level tertiles were positively associated with multiple metabolic phenotypes and circulating inflammatory marker and adipokine levels and negatively associated with high-density lipoprotein cholesterol and adiponectin levels and estimated glomerular filtration rates (eGFRs). Genotype and haplotype analyses showed that RARRES2 SNPs were significantly associated with chemerin, fibrinogen, interleukin 6, and lipocalin 2 levels. Stepwise logistic regression analysis showed that C-reactive protein level, leptin level, triglyceride level, eGFR, rs3735167 genotypes, sex, and soluble P-selectin level were independently associated with chemerin levels. In conclusion, pleiotropic associations were noted between RARRES2 variants, circulating chemerin levels and multiple metabolic phenotypes and inflammatory marker levels. This study provides further evidence for the potential roles of chemerin in metabolic and inflammation-related diseases.

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