Anti-inflammatory effect of β2 adrenergic stimulation on circulating monocytes with a pro-inflammatory state in high-fat diet-induced obesity

Gálvez, Isabel; Martín-Cordero, Leticia; Hinchado, María Dolores; Álvarez-Barrientos, Alberto; Ortega, Eduardo

doi:10.1016/j.bbi.2019.04.042

Cited by 20 publications

(35 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that obesity is a low-grade inflammatory condition [4,5] and, moreover, our group has recently found that monocytes from obese mice present a pro-inflammatory profile and phenotype compared to those from lean mice [34], thus confirming the elevated inflammatory basal set-point of monocytes from obese individuals. As shown in results above, the effect of exercise on the monocyte-mediated inflammatory response was a global anti-inflammatory effect in obese animals, and pro-inflammatory or without changes in lean animals.…”

Section: Resultssupporting

confidence: 63%

“…Systemically, an excessive immune response or inflammatory state normally stimulates a negative feedback stress mechanism, which protects the organism from an “overshoot” of pro-inflammatory cytokines and other inflammatory mediators [21,33]. In obesity, monocytes are in a pro-inflammatory state, and β2 AR stimulation induces a shift towards an anti-inflammatory phenotype and activity profile, whereas it induces a shift towards a pro-inflammatory phenotype and activity profile in monocytes from lean individuals, thus being anti-inflammatory only in the case of an elevated inflammatory status [34]. Thus, high inflammatory basal set-points, like those found in chronic low-grade inflammatory conditions, can determine different effects of β2 AR stimulation on inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Obesity Affects β2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals

et al. 2019

Self Cite

View full text Add to dashboard Cite

Anomalous immune/inflammatory responses in obesity take place along with alterations in the neuroendocrine responses and dysregulation in the immune/stress feedback mechanisms. Exercise is a potential anti-inflammatory strategy in this context, but the influence of exercise on the β2 adrenergic regulation of the monocyte-mediated inflammatory response in obesity remains completely unknown. The first objective of this study was to analyze the effect of exercise on the inflammatory profile and phenotype of monocytes from obese and lean animals, and the second aim was to determine whether obesity could affect monocytes’ inflammatory response to β2 adrenergic activation in exercised animals. C57BL/6J mice were allocated to different lean or obese groups: sedentary, with acute exercise, or with regular exercise. The inflammatory profile and phenotype of their circulating monocytes were evaluated by flow cytometry in the presence or absence of the selective β2 adrenergic receptor agonist terbutaline. Exercise caused an anti-inflammatory effect in obese individuals and a pro-inflammatory effect in lean individuals. β2 adrenergic receptor stimulation exerted a global pro-inflammatory effect in monocytes from exercised obese animals and an anti-inflammatory effect in monocytes from exercised lean animals. Thus, β2 adrenergic regulation of inflammation in monocytes from exercised animals seems to depend on the inflammatory basal set-point.

show abstract

Section: Resultssupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Obesity Affects β2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, clenbuterol could also affect insulin sensitivity through a reduction in inflammation, since these two conditions are closely associated (reviewed in [ 42 , 43 ]). In fact, other β 2 -adrenergic agonists, salbutamol and terbutaline, exhibited anti-inflammatory effects in diabetic rats and DIO mice [ 44 , 45 ]. Ultimately, corrected hyperglycaemia can also improve insulin sensitivity, since glucotoxicity by itself can lead to insulin resistance in healthy men and mice [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment with a β-2-adrenoceptor agonist stimulates glucose uptake in skeletal muscle and improves glucose homeostasis, insulin resistance and hepatic steatosis in mice with diet-induced obesity

et al. 2020

View full text Add to dashboard Cite

Aims/hypothesis Chronic stimulation of β 2-adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of β 2-adrenoceptors. In the current study we further explored the potential therapeutic relevance of β 2-adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect. Methods C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen. Results Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment, p < 0.01) and these effects persisted up to 42 days of treatment. These favourable metabolic effects could be achieved with doses as low as 0.025 mg kg −1 day −1 (40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%, p < 0.001) as well as during chronic treatment in diet-induced obese mice (by 74%, p < 0.001). Notably, prolonged treatment with low-dose clenbuterol improved whole-body insulin sensitivity (glucose disposal rate after insulin injection increased up to 1.38 ± 0.31%/min in comparison with 0.15 ± 0.36%/min in control mice, p < 0.05) and drastically reduced hepatic steatosis (by 40%, p < 0.01) and glycogen (by 23%, p < 0.05). Conclusions/interpretation Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and Anastasia Kalinovich and Nodi Dehvari contributed equally to this study.

show abstract

“…41,60,61 Similarly, several inbred mouse strains, notably C57BL/6J, FVB/N and DBA/2J, are also susceptible to HFD-induced obesity. [62][63][64][65][66][67] Interestingly, a small fraction of rodents are resistant to DIO, although the underlying mechanisms are currently not completely understood. 68,69 However, critical information has been obtained using obesogenic diets for the selection of obesity-prone (OP) or obesity-resistant (OR) or DIO/diet-resistant (DR) rodents using outbred and/or inbred strains, 68,70,71 as will be mentioned throughout the manuscript.…”

Section: Several Complementary Markers Have Been Used To Assess Obesimentioning

confidence: 99%

Diet‐induced rodent models of obesity‐related metabolic disorders—A guide to a translational perspective

et al. 2020

View full text Add to dashboard Cite

Diet is a critical element determining human health and diseases, and unbalanced food habits are major risk factors for the development of obesity and related metabolic disorders. Despite technological and pharmacological advances, as well as intensification of awareness campaigns, the prevalence of metabolic disorders worldwide is still increasing. Thus, novel therapeutic approaches with increased efficacy are urgently required, which often depends on cellular and molecular investigations using robust animal models. In the absence of perfect rodent models, those induced by excessive consumption of fat and sugars better replicate the key aspects that are the root causes of human metabolic diseases. However, the results obtained using these models cannot be directly compared, particularly because of the use of different dietary protocols, and animal species and strains, among other confounding factors. This review article revisits diet-induced models of obesity and related metabolic disorders, namely, metabolic syndrome, prediabetes, diabetes and nonalcoholic fatty liver disease. A critical analysis focused on the main pathophysiological features of rodent models, as opposed to the criteria defined for humans, is provided as a practical guide with a translational perspective for the establishment of animal models of obesity-related metabolic diseases.

show abstract

Anti-inflammatory effect of β2 adrenergic stimulation on circulating monocytes with a pro-inflammatory state in high-fat diet-induced obesity

Cited by 20 publications

References 62 publications

Obesity Affects β2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals

Obesity Affects β2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals

Treatment with a β-2-adrenoceptor agonist stimulates glucose uptake in skeletal muscle and improves glucose homeostasis, insulin resistance and hepatic steatosis in mice with diet-induced obesity

Diet‐induced rodent models of obesity‐related metabolic disorders—A guide to a translational perspective

Contact Info

Product

Resources

About