D-Allulose Reduces Hypertrophy and Endoplasmic Reticulum Stress Induced by Palmitic Acid in Murine 3T3-L1 Adipocytes.

Natural rare sugars are an alternative category of sweeteners with positive physiologic and metabolic effects both in in vitro and animal models. D-allulose is a D-fructose epimer that combines 70% sucrose sweetness with the advantage of an extremely low energy content. However, there are no data about the effect of D-allulose against adipose dysfunction; thus, it remains to be confirmed whether D-allulose is useful in the prevention and in treatment of adipose tissue alterations. With this aim, we evaluated D-allulose's preventive effects on lipid accumulation in 3T3-L1 murine adipocytes exposed to palmitic acid (PA), a trigger for hypertrophic adipocytes. D-allulose in place of glucose prevented adipocyte hypertrophy and the activation of adipogenic markers C/EBP-ß and PPARγ induced by high PA concentrations. Additionally, D-allulose pretreatment inhibited the NF-κB pathway and endoplasmic reticulum stress caused by PA, through activation of the Nrf2 pathway. Interestingly, these effects were also observed as D-allulose post PA treatment. Although our data need to be confirmed through in vivo models, our findings suggest that incorporating D-allulose as a glucose substitute in the diet might have a protective role in adipocyte function and support a unique mechanism of action in this sugar as a preventive or therapeutic compound against PA lipotoxicity through the modulation of pathways connected to lipid transport and metabolism.

An overview on the cellular mechanisms of anthocyanins in maintaining intestinal integrity and function.

Structural and functional changes of the intestinal barrier, as a consequence of a number of (epi)genetic and environmental causes, have a main role in penetrations of pathogens and toxic agents, and lead to the development of inflammation-related pathological conditions, not only at the level of the GI tract but also in other extra-digestive tissues and organs. Anthocyanins (ACNs), a subclass of polyphenols belonging to the flavonoid group, are well known for their health-promoting properties and are widely distributed in the human diet. There is large evidence about the correlation between the human intake of ACN-rich products and a reduction of intestinal inflammation and dysfunction. Our review describes the more recent advances in the knowledge of cellular and molecular mechanisms through which ACNs can modulate the main mechanisms involved in intestinal dysfunction and inflammation, in particular the inhibition of the NF-κB, JNK, MAPK, STAT3, and TLR4 proinflammatory pathways, the upregulation of the Nrf2 transcription factor and the expression of tight junction proteins and mucins.

Low concentrations of α-lipoic acid reduce palmitic acid-induced alterations in murine hypertrophic adipocytes.

Obesity is a metabolic disorder with excessive body fat accumulation, increasing incidence of chronic metabolic diseases. Hypertrophic obesity is associated with local oxidative stress and inflammation. Herein, we evaluated the in vitro activity of micromolar concentrations of α-lipoic acid (ALA) on palmitic acid (PA)-exposed murine hypertrophic 3T3-L1 adipocytes, focussing on the main molecular pathways involved in adipogenesis, inflammation, and insulin resistance. ALA, starting from 1 µM, decreased adipocytes hypertrophy, reducing PA-triggered intracellular lipid accumulation, PPAR-γ levels, and FABP4 gene expression, and counteracted PA-induced intracellular ROS levels and NF-κB activation. ALA reverted PA-induced insulin resistance, restoring PI3K/Akt axis and inducing GLUT-1 and glucose uptake, showing insulin sensitizing properties since it increased their basal levels. In conclusion, this study supports the potential effects of low micromolar ALA against hypertrophy, inflammation, and insulin resistance in adipose tissue, suggesting its important role as pharmacological supplement in the prevention of conditions linked to obesity and metabolic syndrome.

Low concentrations of antimony impair adipogenesis and endoplasmic reticulum homeostasis during 3T3-L1 cells differentiation.

Antimony (Sb) is a metalloid widely present in plastics used for food contact packaging, toys and other household items. Since Sb can be released by these plastics and come into contact with humans, health concerns have been highlighted. The effect of Sb on human tissues is yet controversial, and biochemical mechanisms of toxicity are lacking. In the present study, the effect of very low nanomolar concentrations of Sb(III), able to mimicking chronic human exposure, was evaluated in 3T3-L1 murine cells during the differentiation process. Low nanomolar Sb exposure (from 0.05 to 5 nM) induced lipid accumulation and a marked increase in C/EBP-ß and PPAR-γ levels, the master regulators of adipogenesis. The Sb-induced PPAR-γ was reverted by the estrogen receptor antagonist ICI 182,780. Additionally, Sb stimulated preadipocytes proliferation inducing G2/M phase of cell cycle and this effect was associated to reduced cell-cycle inhibitor p21 levels. In addition to these metabolic dysfunctions, Sb activated the proinflammatory NF-κB pathway and altered endoplasmic reticulum (ER) homeostasis inducing ROS increase, ER stress markers XBP-1s and pEIF2a and downstream genes, such as Grp78 and CHOP. This study, for the first time, supports obesogenic effects of low concentrations exposure of Sb during preadipocytes differentiation.

Regulation of mitotic clonal expansion and thermogenic pathway are involved in the antiadipogenic effects of cyanidin-3-O-glucoside.

Introduction: Obesity is a metabolic disease with an increase both in cell size (hypertrophy) and in cell number (hyperplasia) following differentiation of new adipocytes. Adipogenesis is a well-orchestrated program in which mitotic clonal expansion (MCE) occurs in the early step followed by the late terminal differentiation one. Methods: Aim of the study was to evaluate the in vitro effects of cyanidin-3-O-glucoside (C3G), an anthocyanin present in many fruits and vegetables, in the early or late phase of 3T3-L1 preadipocytes differentiation. Results: C3G exposure in the early phase of adipogenesis process induced a more marked reduction of CCAAT/enhancer-binding protein-ß (C/EBPß), peroxisome proliferator-activated receptor γ (PPAR-É£) and fatty acid synthase (Fasn) expression than late phase exposure and these effects were associated to a reduced MCE with cell cycle arrest at G0/G1 phase via p21 expression. Furthermore, C3G exposure during the early phase activated AMP-activated protein kinase (AMPK) pathway better than in the late phase promoting the enhancement of beige-like adipocytes. In fact, C3G induced thermogenic biomarkers uncoupling protein-1 (Ucp1) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (Pgc1) and these effects were more evident during early phase exposure. Conclusion: Our data demonstrate that C3G reduces the terminal adipogenic process affecting the early phase of differentiation and inducing a thermogenic program.

Efficacy of Two Moroccan Cistus Species Extracts against Acne Vulgaris: Phytochemical Profile, Antioxidant, Anti-Inflammatory and Antimicrobial Activities.

BACKGROUND: The genus Cistus L. (Cistaceae) includes several medicinal plants growing wild in the Moroccan area. Acne vulgaris (AV) is a chronic skin disorder treated with topical and systemic therapies that often lead to several side effects in addition to the development of antimicrobial resistance. Our study aimed to investigate the bioactivity of extracts of two Moroccan Cistus species, Cistus laurifolius L. and Cistus salviifolius L., in view of their use as potential coadjuvants in the treatment of mild acne vulgaris. METHODS: Targeted phytochemical profiles obtained by HPLC-DAD and HPLC-ESI/MS analyses and biological activities ascertained by several antioxidants in vitro chemical and cell-based assays of the leaf extracts. Moreover, antimicrobial activity against Gram-positive and Gram-negative bacteria, and Candida albicans was evaluated. RESULTS: Analyses revealed the presence of several polyphenols in the studied extracts, mainly flavonoids and tannins. Cistus laurifolius L. and Cistus salviifolius L. possessed good biological properties and all extracts showed antibacterial activity, particularly against Staphylococcus aureus, S. epidermidis, and Propionibacterium acnes, identified as the main acne-causing bacteria. CONCLUSION: The results suggest that examined extracts are promising agents worthy of further studies to develop coadjuvants/natural remedies for mild acne treatment.

The p-Phthalates Terephthalic Acid and Dimethyl Terephthalate Used in the Manufacture of PET Induce In Vitro Adipocytes Dysfunction by Altering Adipogenesis and Thermogenesis Mechanisms.

Public health concerns associated with the potential leaching of substances from Polyethylene terephthalate (PET) packaging have been raised due to the role of phthalates as endocrine-disrupting chemicals or obesogens. In particular, changes in the environment such as pH, temperature, and irradiation can improve contaminant migration from PET food packaging. In this study, the in vitro effects of p-phthalates terephthalic acid (TPA) and dimethyl terephthalate (DMT) on murine adipocytes (3T3-L1) were evaluated using concentrations that might be obtained in adult humans exposed to contaminated sources. TPA and, in particular, DMT exposure during 3T3-L1 differentiation increased the cellular lipid content and induced adipogenic markers PPAR-γ, C/EBPß, FABP4, and FASN, starting from low nanomolar concentrations. Interestingly, the adipogenic action of TPA- and DMT-induced PPAR-γ was reverted by ICI 182,780, a specific antagonist of the estrogen receptor. Furthermore, TPA and DMT affected adipocytes' thermogenic program, reducing pAMPK and PGC-1α levels, and induced the NF-κB proinflammatory pathway. Given the observed effects of biologically relevant chronic concentrations of these p-phthalates and taking into account humans' close and constant contact with plastics, it seems appropriate that ascertaining safe levels of TPA and DMT exposure is considered a high priority.