Anthocyanins ameliorate palmitate‐induced inflammation and insulin resistance in 3T3‐L1 adipocytes

Abstract

Increased adiposity has been associated with adipose tissue low‐grade inflammation leading to insulin resistance. Adipocyte differentiation inhibitors are expected to be effective in preventing obesity and related diseases. Anthocyanins (ACNs) are associated to enhanced adipocyte function and protection from metabolic stress. Herein, we evaluated the in vitro protective effects of an ACN rich extract against palmitic acid (PA)‐induced hypertrophy, inflammation, and insulin resistance in 3T3‐L1 adipocytes. ACN extract pretreatment reduces lipid accumulation and peroxisome proliferators‐activated receptor‐γ protein levels induced by PA. In addition, PA induces inflammation with activation of NF‐κB pathway, whereas ACN extract pretreatment dose‐dependently inhibited this pathway. Furthermore, adipocyte dysfunction associated with hypertrophy induces insulin resistance by affecting phosphatidylinositol 3‐kinase‐protein kinase B/Akt axis, GLUT‐1, and adiponectin mRNA levels. ACN extract pretreatment reverts these effects induced by PA and moreover was able to induce insulin pathway with levels higher than insulin control cells, supporting an insulin sensitizer role for ACNs. This study demonstrates a prevention potential of ACNs against obesity comorbidities, due to their protective effects against inflammation/insulin resistance in adipocytes. In addition, these results contribute to the knowledge and strategies on the evaluation of the mechanism of action of ACNs from a food source under basal and insulin resistance conditions related to obesity.

In Vitro Effects of Cyanidin‐3‐O‐Glucoside on Inflammatory and Insulin‐Sensitizing Genes in Human Adipocytes Exposed to Palmitic Acid

“…In fact, in murine 3T3-L1 exposed to PA we have shown the ability of C3G, as well as of an anthocyanin-rich extract, to counteract the activation of NF-кB pathway, the master regulator of inflammatory machinery, induced by an excess of this FFA. [18,19] Moreover, the anti-inflammatory activity of anthocyanins has been also demonstrated in 3T3-L1 adipocytes exposed to TNF-α through the inhibition of NF-кB pathway as well as through the increase of adiponectin and the reduction of leptin, two markers considered as inflammatory modulators known to play a crucial role in insulin sensitivity and body energy balance. [38,40] However, articles reporting the effects of C3G on murine adipocytes demonstrated that the minimum effective C3G concentration was > 5 μM.…”

“…A wide range of biological activities of anthocyanins has been reported in animal models, including antioxidant, anti‐inflammatory, anti‐atherosclerosis, and anti‐hyperglycemic activities [17] . In two recent studies we demonstrated that both cyanidin‐3‐ O ‐glucoside (C3G) and an anthocyanin rich extract showed not only a high antioxidant and anti‐inflammatory activity, but also a marked anti‐obesity and insulin sensitizing effect, markedly reducing hypertrophy, inflammation, and insulin resistance induced by high concentration of FFAs in murine 3T3‐L1 adipocytes [18,19] …”

“…[17] In two recent studies we demonstrated that both cyanidin-3-O-glucoside (C3G) and an anthocyanin rich extract showed not only a high antioxidant and anti-inflammatory activity, but also a marked antiobesity and insulin sensitizing effect, markedly reducing hypertrophy, inflammation, and insulin resistance induced by high concentration of FFAs in murine 3T3-L1 adipocytes. [18,19] However, these data, as well as most of the information on the molecular mechanisms altered in obesity, are mainly based on in vitro studies performed on cells of murine origin. There are, indeed, important limitations on these in vitro models due to the interspecies differences between mice and humans in proteins and adipokines expression and in the adipogenesis process.…”

A Review of the Properties of Anthocyanins and Their Influence on Factors Affecting Cardiometabolic and Cognitive Health

“…When HAEC were exposed to the series of anthocyanins and respective metabolites, they found a reduction of ICAM-1 and VCAM-1 mRNA by the anthocyanins, with a reduction in IL-6 mRNA by the metabolites [ 66 ]. Palmitate-induced inflammation was also studied by Muscara et al (2019) in murine adipocytes [ 67 ]. They found that anthocyanins specifically from bilberry ( Vaccinium myrtillus ) and blackcurrant ( Ribes nigrum ) had a dose-dependent attenuating effect on NF-kB and IL-6 mRNA level.…”

The Influence of Supplementation of Anthocyanins on Obesity-Associated Comorbidities: A Concise Review

“…Anthocyanins treatment suppressed lipid accumulation, PPAR-γ level, and NF-κB activation in palmitic acid-induced 3T3-L1 adipocytes in a dose-dependent manner. Moreover, anthocyanins treatment improved insulin sensitivity and suppressed the comorbidities of obesity in vitro [ 83 ]. Cyanidin and C3G-rich ethanolic extract of Vigna unguiculata showed significant pancreatic lipase inhibition in vitro, which indicated that V. unguiculata anthocyanins have anti-obesity potential [ 84 ] ( Table 3 ).…”