Differential effects of GLP-1 receptor agonist on foam cell formation in monocytes between non-obese and obese subjects

Tanaka, Masashi; Matsuo, Yoshiyuki; Masuda, Shinji; Terada, Yuko; Muranaka, Kazuya; Wada, Hiromichi; Hasegawa, Koji; Shimatsu, Akira; Satoh‐Asahara, Noriko

doi:10.1016/j.metabol.2015.10.009

Cited by 31 publications

(24 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, GLP-1R is expressed in some lineages of immune cells that have an immunomodulatory role in the migration and differentiation of T and B lymphocytes [16,55,56]. GLP-1R also displays anti-atherogenic effects during obesity by reducing monocyte/macrophage migration and in ammatory cytokine production [57,58]. In this study, we observed a reduced expression of GLP-1R in obese children and adolescents.…”

Section: Discussionsupporting

confidence: 53%

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Vargas-Sánchez¹,

Vargas²,

Urrutia³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by obesity directly affects the metabolism of various tissues. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors and transcription factors essential for energy homeostasis of different tissues. Despite its wide-ranging expression and function, the functional mismatch of the PPAR subtypes establish biological mechanisms responsible for metabolic diseases from childhood. In addition, the glucagon-like peptide-1 receptor (GLP-1R) activation can influence insulin secretion, but also the cytokine profile possibly mediated through PPARγ activation. However, to date, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients has been unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population. Results Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, A/G index, and HOMA score when compared to the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p = 0,0081), IL-6 (p = 0,0005), TNF-α (p = 0,0004), IFN-γ (p = 0,0110), MCP-1 (p = 0,0452), and adipsin (p = 0,0397), whereas displayed a reduction of adiponectin (p = 0,0452). The expression of PPARα and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPARα correlates negatively with TNF-α (p = 0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPARβ/δ expression was similar between groups, it was negatively associated with IL-8 levels (p = 0,0085). Conclusions PPARα and PPARβ/δ expression are negatively associated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation observed in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese children and adolescents, and both receptors are associated with the abdominal skinfold suggesting a role in fat distribution that could indirectly affect the function of different immune cells and the secreted cytokines. Thereby, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.

show abstract

Section: Discussionsupporting

confidence: 53%

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Vargas-Sánchez¹,

Vargas²,

Urrutia³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The GLP-1 agonist exendin-4 induced autophagy in monocytes from non-obese subjects which suppresses foam cell formulation but appear to have the opposite effects in monocytes from obese patients in a small study of 10 Japanese patients 149 . Further research is necessary as this does not seem consistent with the overall decrease in cardiovascular adverse outcomes seen in clinical trials of other GLP-1 agonists such as a large randomized controlled trial of liraglutide in 9340 patients 150 and semaglutide in 3297 patients 151 .…”

Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 97%

Macrophage functions in lean and obese adipose tissue

2017

View full text Add to dashboard Cite

Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

show abstract

“…299,300 Peptide hormones appear to play an important role in transferring luminal signals during obesity, be it nutritional or microbial, to the immune system. GLP-1 agonists can inhibit monocyte to foam cell transition via altering autophagy, but this occurs only in obese patients, 301 placing eecs under the spot light in this growing epidemic.…”

Section: Direct Immune Modulationmentioning

confidence: 99%

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

2018

View full text Add to dashboard Cite

The intestinal epithelium must balance efficient absorption of nutrients with partitioning commensals and pathogens from the bodies' largest immune system. If this crucial barrier fails, inappropriate immune responses can result in inflammatory bowel disease or chronic infection. Enteroendocrine cells represent 1% of this epithelium and have classically been studied for their detection of nutrients and release of peptide hormones to mediate digestion. Intriguingly, enteroendocrine cells are the key sensors of microbial metabolites, can release cytokines in response to pathogen associated molecules and peptide hormone receptors are expressed on numerous intestinal immune cells; thus enteroendocrine cells are uniquely equipped to be crucial and novel orchestrators of intestinal inflammation. In this review, we introduce enteroendocrine chemosensory roles, summarize studies correlating enteroendocrine perturbations with intestinal inflammation and describe the mechanistic interactions by which enteroendocrine and mucosal immune cells interact during disease; highlighting this immunoendocrine axis as a key aspect of innate immunity.

show abstract

Differential effects of GLP-1 receptor agonist on foam cell formation in monocytes between non-obese and obese subjects

Cited by 31 publications

References 44 publications

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Macrophage functions in lean and obese adipose tissue

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

Contact Info

Product

Resources

About