BackgroundAnti-freeze Glycoproteins (AFGPs) were described to preserve biological materials and protect them from different stresses.AimsThe effects of a synthetic anti-freeze glycoprotein-based compound, TFC-1326, on human skin quality and its biological actions were studied.MethodsThe effects of various concentrations of TFC-1326 on the biology of human preadipocytes, differentiated in the proinflammatory microenvironment, and on human fibroblasts grown in coculture with human mature adipocytes or monocultured in stress conditions were investigated in, in vitro studies. Additionally, the efficacy of a 1% TFC-1326 topical cream was evaluated in a clinical investigation on the skin biology and appearance of 20 women aged between 40 and 65 years throughout 84 days of application.ResultsThe in vitro studies revealed that TFC-1326 mitigated the deleterious effects of a proinflammatory cytokine cocktail produced by human macrophages, by restoring preadipocyte adipogenic capacity and by reducing their fibroinflammatory state. TFC-1326 also stimulated the proliferative capacity of dermal fibroblasts co-cultured with mature adipocytes as well as their production of hyaluronic acid and procollagen type I, while decreasing IL6 secretion and increasing fibroblast viability. Furthermore, daily 1% TFC-1326 topical cream application, measurably improved skin radiance and laxity, as well as skin density. Finally, significant reductions of the volume and depth of the crow's feet wrinkles were also observed.ConclusionsThe compound TFC-1326 significantly improved the physiological appearance and cellular functions of aging skin.

Abstract Background Sinetrol® Xpur is a polyphenolic ingredient rich in citrus flavonoids that has shown weight loss effects in previous studies. The dose dependent nature, gut microbial actions of this product has not been explored previously, thus presented in this study. Methods In this open label study, we evaluated the effect of Sinetrol® Xpur supplementation on healthy but overweight/obese adults (20–50 yrs) for 16 weeks. Participants (n = 20) were randomly allocated to a high dose group (HD, 1800 mg/day) or low dose group (LD, 900 mg/day) of the product for 16 weeks. Fat composition, gut microbial composition, were evaluated using MRI and 16S rDNA sequencing respectively at week 1 and 16. Results We observed HDL, HbA1C, LDL and leptin improved significantly over 16 weeks, irrespective of the dosage. There was a trend for decrease in visceral adipose tissue (VAT), BMI over time and body weight displayed a trend for dose dependent decrease. Eubacterium xylanophilum, Ruminococcacea UCG-004 genus which increased in HD and LD respectively were negatively associated to VAT. Both doses increased butyrate producers such as Eubacterium ruminantium and Ruminococcaceae NK4A214 genus. Conclusions Overall chronic supplementation of Sinetrol® Xpur, irrespective of their dose improved HDL, HbA1c, LDL and leptin and tended to decrease visceral adipose tissue via changes in gut microbiota. Trial registration number NCT03823196.

Background and Objectives: Excessive deposits of white adipose tissue lead to obesity. Preadipocyte differentiation, adipocyte metabolism, and some inflammatory and profibrotic factors are key in modulating early fat mass expansion and chronic low-grade inflammation and could be targeted to prevent child obesity. Plant-based proteins are being increasingly used, and we evaluated the potential impact on adipose cell biology and the inflammatory processes of some of them, after simulated in vitro gastrointestinal digestion, on (1) the human preadipocyte differentiation, (2) their fibro-inflammatory state, (3) the metabolism of human mature adipocytes, and (4) the beiging potential of two selected digestates on preadipocytes. Methods: (a) Preadipocytes and (b) mature adipocytes isolated from human subcutaneous adipose tissues were treated with eight plant-based protein digestates (PBPDs) and one animal-based protein digestate for (a) 7 to 11 days or (b) 24 h, respectively. We assessed (a) their effects on preadipocytes, in proadipogenic ± proinflammatory conditions, by evaluating cytotoxicity, cell number, lipid droplet accumulation, adiponectin secretion, and UCP1 expression on the one hand, and IL6, CCL2, and fibronectin secretions on the other hand, and (b) their effects on adipocyte metabolism by studying cytotoxicity, lipolysis activity, and adiponectin secretion. Results: Six PBPDs stimulated adiponectin’s secretion by the preadipocytes without affecting their viability and differentiation capacities at the tested doses. Similarly, we observed no cytotoxicity effects on mature adipocytes and a dose-dependent increase in their adiponectin secretion for treatment with five PBPDs. One PBPD modulated the lipolytic activity of adipocytes by decreasing the release of glycerol. In proinflammatory conditions, seven PBPDs reduced the number of preadipocytes, which is abnormally increased with inflammation. Two of them were able to decrease the CCL2 chemokine secretion, and one of them reduced the production of fibronectin, a potential pro-fibrotic protein. Finally, two selected PBPDs were able to increase beige differentiation (UCP1 expression) of preadipocytes cultured in proadipogenic conditions. Discussion: This study revealed potential benefits of plant proteins for obesity prevention, and specifically highlighted the respective properties of pea and oat proteins prototypes: increasing adiponectin secretion and beige differentiation in preadipocytes; decreasing pro-inflammatory and fibrotic molecules secretion by proinflammatory preadipocytes and regulating basal lipolysis and increasing adiponectin secretion by mature adipocytes.

Purpose Excessive fat mass accumulation in obesity leads to diverse metabolic disorders, increased risks of cardiovascular diseases and in some cases, mortality. The aim of this study was to screen the actions of botanical extracts intended for oral use on human adipose tissue, using an in vitro screening model combining human intestinal cells with human adipose cells. This was to find the most effective extracts on lipid accumulation, UCP1 expression and ATP production in pre-adipocytes and on adipocyte lipolysis. Methods In this study, 25 individual plant extracts were screened for their effects on human adipose cells. Consequently, an original in vitro model was set up using the Caco-2 cell line, to mimic the intestinal passage of the extracts and then exposing human adipose cells to them. The biological actions of extracts were thus characterized, and compared with a coffee extract standard. The most effective extracts, and their combinations, were retained for their actions on lipid accumulation, the expression of the thermogenic effector UCP1 and ATP production in pre-adipocytes as well as on lipolysis activity of mature adipocytes. Results The biphasic culture system combining human Caco-2 cells with human adipose cells was verified as functional using the green coffee extract standard. Out of the 25 plant extracts studied, only 7 and their combinations were retained due to their potent effects on adipose cells biology. The data showed that compared to the coffee extract standard, Immortelle, Catechu, Carrot and Rose hip extracts were the most effective in reducing lipid accumulation and increased UCP1 expression in human pre-adipocytes. Conclusion This study reveals the potential inhibitory effects on lipid accumulation and thermogenic activity of Immortelle, Catechu, Carrot and Rose hip extracts, and for the first time synergies in their combinations, using an in vitro model mimicking as closely as possible, human intestinal passage linked to adipose cells. These findings need to be confirmed by in vivo trials.

Background Purple tulip extract is a rich source of flavonoids which are powerful antioxidants and can hence be considered as an ideal candidate for use in skin care products. Aims We aimed to evaluate the effects of purple tulip extract on skin quality and to determine its molecular modes of interaction. Methods A pangenomic study on human skin fibroblasts was carried out to analyze multiple changes in gene expression. Ex vivo studies of human skin explants exposed to ultraviolet (UV) irradiation or H(2)O(2)were performed to assess modulations of protein expression. Finally, a clinical assay was carried out to evaluate the efficacy of purple tulip extract on skin appearance and condition of aged women. Results Genetic modulation analyses led us to infer the induction of many biological functions including cell differentiation, proliferation, migration, inflammatory responses, and matrix remodeling. The ex vivo studies revealed an enhancement of the collagen network and increased expression of glycosaminoglycans (GAG), fibronectin, and collagen VI. Finally, the clinical study highlighted the potential anti-aging properties of the purple tulip extract which decreased the relaxation of the oval face and improved skin elasticity after 28 days of treatment. Significant reductions of the length and depth of the nasolabial wrinkles were also observed. Conclusion Our genomics data on the effect of purple tulip extract on the ex vivo UV-challenged skin showed that genes responsible for, among others, the upkeep of the skin, such as collagen induction, immune cell proliferation, and epidermal repair, were all up-regulated. More importantly, the clinical study corroborated these data by the visible and measurable effects of the topical purple tulip extract on the aged skin of 22 women, further demonstrating the beneficial impact of the extract on aged skin.

The beneficial role of subcutaneous adipose tissue in skin rejuvenation derived from its capacity to fill the under-layer volumes but also from its ability to regulate the extracellular matrix production by dermis fibroblasts. Hyaluronic acid (HA), a major component of the extracellular matrix, is a commonly used injectable dermal filler showing excellent efficiencies to maintain tissue augmentation even after its biodegradation. To improve their stability, the HA molecules can also be "cross-linked" to each other. The effects of cross-linked HA-based fillers on the dermal structure are well known. For safety reasons, most of the physicians prefer to use the blunt cannula for injections. However, evidences showed that the cannula could not be located in the dermis, but it passes through immediate hypodermis and the long-lasting effect of cross-linked HA-based fillers may be related to its effects on adipose tissue. To test whether cross-linked HA has a direct effect on human adipocytes, we treated isolated adipocytes and precursors cells from human skin donors with cross-linked HA. Biochemical and cellular analysis demonstrated that treatment by cross-linked HA showed beneficial effects on differentiated cell adherence and survival as well as reduced basal and induced lipolysis in fully mature adipocytes. Taken together, these data showed that cross-linked HA promoted cell adherence and preserved the adipogenic capacity of preadipocytes during prolonged cell culture, bringing additional evidences of the beneficial role of cross-linked HA-based fillers in maintenance of the subcutaneous fat mass. This first study could defend a preventive approach to facial volume loss during natural aging.

BACKGROUND:The leaves of Tasmannia lanceolata mainly contain polygodial that is known to exhibit a range of biological functions including anti-inflammatory effects. AIMS:These studies aimed to assess the effects of Tasmannia lanceolata extract (TLE) on skin and more particularly on stretch marks in women. PATIENTS/METHODS:A double-blind, randomized, placebo-controlled clinical study was carried out on 29 women, aged from 25 to 60 years, to investigate the effects of TLE on stabilized stretch marks. TLE and placebo products were topically applied daily for 8 weeks. Skin roughness and firmness of stretch marks were assessed by 2D and 3D photograph processing and analyses. Dermal density and thickness were evaluated using ultrasound, while stretch mark conditions (length, color, and depth) were determined by clinical scoring. Matricial proteins (pro-collagen I and elastin) and pro-matricial factors, like TGF-β concentrations, were quantified from cultures of human skin explants presenting stretch marks, treated with TLE or vehicle control. RESULTS:Skin roughness of stretch marks was significantly reduced in the TLE group after 8 weeks of treatment. Skin firmness of stretch marks was significantly increased in the TLE group after 4 weeks of treatment, and this improved effect was maintained until the end of the study. Dermal density and thickness were significantly increased in the TLE group compared to the placebo group. Furthermore, TLE restored the dermal condition of the stretch mark skin, up to normal skin levels. In addition, pro-collagen I and elastin concentrations were found to be higher in the TLE-treated stretch mark skin explants compared to the untreated ones, associated with higher quantities of TGF-β production. CONCLUSION:These results revealed that TLE could help improve the aspect of stabilized stretch marks in women by restoring the matricial environment.

Background: Polar lipids from wheat (Triticum vulgare/aestivum) extract oil (WEO) are known to improve skin hydration. Aims: These studies aimed to assess WEO benefits on the skin appearance of middle-aged women. Methods: A double-blind, randomized, placebo-controlled clinical study was carried out on 64 healthy women, aged from 45 to 60 years, to investigate antiaging effects and benefits for the skin. The study lasted 20 weeks including 12 weeks of oral supplementation with WEO or placebo and 8 weeks of follow-up. Wrinkles in the "crow's-feet" area were evaluated by the Lemperle score. Skin hydration was measured using a corneometer, while roughness and radiance were determined by clinical scoring. Collagen content was quantified in human skin explants exposed to ultraviolet (UV) irradiations and treated with WEO or vehicle control. Results: Compared to the placebo group, the Lemperle score was significantly reduced in the WEO group between W0 and W8 to reach a clinically significant 1 grade at W12. Facial hydration was significantly improved in the WEO group from W0 to W12, whereas leg hydration was significantly increased after 4 weeks and lasted throughout the supplementation period. Skin roughness and radiance were also significantly improved from W0 to W8 in the WEO group compared to placebo group. A higher collagen content was measured in the UV-irradiated skin explants treated with WEO compared to the untreated ones. Conclusion: These results confirmed the moisturizing effect of WEO and, for the first time, revealed its potential antiaging properties.

Background Miliacin, the main triterpenoid from millet, is known to stimulate keratinocyte metabolism and proliferation. Polar lipids are able to form vesicles with active compounds and to improve their bioavailability. Objectives We aimed to demonstrate potential benefits of a solution of miliacin encapsulated within polar lipids (MePL) on telogen effluvium prevention and hair condition in women. METHODS After preliminary cell proliferation studies, a placebo-controlled, multicentric, randomized, double-blind trial was performed on sixty-five nonmenopausal women affected by telogen effluvium, to assess the efficacy of a 12-week oral supplementation with MePL. Telogen and anagen densities were determined by phototrichogram analysis. Scalp dryness and hair brightness were clinically evaluated using a Likert scale. Results MePL further enhanced cell proliferation in hair bulb from human scalp than miliacin alone. Compared to the placebo treatment, MePL supplementation significantly reduced telogen density after 12 weeks of treatment. An increase of anagen density was observed in both groups, although there was no significant difference between the two treatments. Scalp dryness was more decreased in the MePL group than in the placebo group. A better improvement of hair brightness was also observed after 12 weeks of supplementation with MePL. Conclusion Twelve weeks of MePL supplementation significantly reduced the hair density in the telogen phase and, in parallel, improved scalp dryness and hair condition. These effects could be linked to MePL activity on cell proliferation in hair bulb. MePL is an original association of plant extract that could help to prevent and/or limit hair loss in women.

Background: The adjunction of platelet-rich plasma with graft fat has been the subject of a few clinical trials which have demonstrated its value in adipocyte survival. The aim of this study was to assess the different efficacies between activated and non-activated PRP on adipose cells in vitro and for adipose tissue graft survival in vivo. Methods: The in vitro study assessed the effects of PRP on both the proliferation and adipocyte differentiation of adipose cells. For the in vivo study, 8 nude rats received 3 human fat injections as follows: 0.8 mL of fat + 0.2 mL of normal saline; 0.8 mL of fat + 0.2 mL of non-activated PRP; and 0.8 mL of fat + 0.2 mL of PRP activated with calcium chloride (CaCl2). The quantitative assessment of adipocyte survival was implemented after 3 months using histomorphometric analysis. Histological and immunohistochemical analysis were also performed to evaluate angiogenesis, inflammation and quality of adipocytes in the grafted tissue. Results: We showed that activated PRP stimulated, in vitro, proliferation and differentiation of adipose cells. In vivo experiments indicated that CaCl2-activated PRP was more efficient than non-activated to prolong the survival of fat grafts in nude rats. The mean percentage areas occupied by viable adipocytes in the PRP-free group, non-activated PRP group and activated PRP group were 13%, 14% and 24% (p = 0.05%), respectively. Histological and immunohistochemical analysis revealed protective effect of activated PRP on inflammation and adipocyte death. Conclusion: This study showed that activation by CaCl2 improves the beneficial effects of PRP for fat graft maintenance. (C) 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

SCOPE:Obesity-related metabolic syndrome is often associated with a decrease of insulin sensitivity, inducing several modifications. However, dietary antioxidants could prevent insulin resistance. We have previously shown the preventive effects of a melon superoxide dismutase (SOD) in obese hamsters. However, its antioxidant effects have never been studied on adipose tissue.METHODS AND RESULTS:We evaluated the effects of a 1-month curative supplementation with SODB on the adipose tissue of obese hamsters. Animals received either a standard diet or a cafeteria diet for 15 wk. Cafeteria diet induced obesity and related disorders, including insulin resistance and oxidative stress, in the abdominal adipose tissue. After SODB supplementation, the adipose tissue weight was decreased, probably by activating adipocytes lipolysis and thus reducing their size. SODB treatment also resulted in abdominal adipose tissue fibrosis reduction. Finally, SODB administration increased the expression of endogenous antioxidant enzymes and thus reduced oxidative stress and insulin resistance. The improvement of insulin sensitivity observed after SODB treatment could explain adipocyte lipolysis activation and fibrosis reduction.CONCLUSION:These findings demonstrate that a dietary SOD supplementation could be a useful strategy against obesity-related modifications in adipose tissue.

To investigate the remineralisation of chitosan pre-treated enamel white spot lesions (WSLs) by bioglass in the presence of the pellicle layer.50 artificial enamel white spot lesions were created by acidic gel. Two lesions were used to investigate the formation of the pellicle layer by treating with human whole saliva for 3 min. 48 lesions were assigned to 6 experimental groups (n = 8): (1) bioactive glass slurry, (2) bioactive glass containing polyacrylic acid (BG + PAA) slurry, (3) chitosan pre-treated WSLs with BG slurry (CS-BG), (4) chitosan pre-treated WSLs with BG + PAA slurry (CS-BG + PAA), (5) “standard” remineralisation solution (RS) and (6) de-ionised water (negative control, NC). Remineralisation was carried out using a pH-cycling model for 7 days. Before each treatment using remineralising agents, 3-min pellicle was formed on lesions’ surfaces. Mineral content changes, surface and subsurface microhardness and ultrastructure were evaluated by Raman intensity mapping, Knoop microhardness and scanning electron microscopy, respectively. Data were statistically analysed using one-way ANOVA with Tukey’s test (p < 0.05 is considered as significant).Despite the heterogeneously formed pellicle layer, all groups showed an increase in surface mineral content after pH-cycling. Chitosan pre-treatment enhanced the subsurface remineralisation of WSLs using bioglass as both pre-treated groups showed greater surface and subsurface microhardness compared to NC. CS-BG exhibited denser subsurface structure than BG, while in CS-BG + PAA the crystals were bigger in size but resemble more enamel-like compared to BG + PAA as shown in SEM observations. Remineralisation of RS was limited to the surface as no significant subsurface changes of mechanical properties and structure were found.Chitosan pre-treatment can enhance WSL remineralisation with bioglass biomaterials when a short-term salivary pellicle is present. A further investigation using a long-term pH-cycling model with mature pellicle is suggested with regards to clinical application.Chitosan pre-treatment has the potential in clinical application to remineralise subsurface lesions to achieve lesion consolidation.

L’arthrose est une maladie chronique, d’évolution généralement lente et évolutive, dans laquelle les compléments alimentaires peuvent avoir un rôle intéressant. Le pharmacien d’officine est en première ligne pour prodiguer conseils et informations. Sans parler de prévention vis-à-vis de l’évolution de la maladie, le renforcement du cartilage favorise le confort du patient et diminue la douleur. Les actifs efficaces sont nombreux mais leur utilisation requiert des précautions.Osteoarthritis is a chronic disease, whose evolution is generally slow and progressive, and for which food supplements can be beneficial. The community pharmacist is on the front line in offering advice and information. As well as helping to prevent the progression of the disease, strengthening the cartilage improves the patient's comfort and reduces pain. There are numerous effective active substances but certain precautions should be taken with regard to their use.

CONTEXT:Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity.OBJECTIVE:Our objective was to identify clinically relevant forms of cathepsin in human obesity.DESIGN AND SETTING:We conducted a prospective study on two independent cohorts.PARTICIPANTS AND INTERVENTIONS:The first cohort includes 45 obese women eligible for gastric surgery (age, 39 +/- 1.6 yr; body mass index, 47 +/- 0.99 kg/m(2)) and 17 nonobese women (age, 38 +/- 1.8 yr; body mass index, 21 +/- 0.44 kg/m(2)). The second cohort comprises 29 obese women (age, 57 +/- 0.8 yr; body mass index, 34 +/- 0.69 kg/m(2)) undergoing 6 months of medically supervised caloric restriction.MAIN OUTCOMES:Cathepsin S, L, and K mRNA levels were determined in surgical adipose tissue biopsies. The proteins were measured in conditioned medium of adipose tissue explants and in circulation.RESULTS:Obese subjects had a 2-fold increase in cathepsin S mRNA in adipose tissue as compared with normal-weight subjects and an increased rate (1.5-fold) of cathepsin S release in adipose tissue explants. Cathepsin S circulating concentrations were increased with obesity (+30%) and reduced after weight reduction (P < 0.05 for both). By contrast, cathepsin L was unaffected in adipose tissue and serum; cathepsin K was undetectable in circulation and unchanged in adipose tissue.CONCLUSION:In humans, cathepsin S is more influenced than cathepsins L and K by changes in energy balance in adipose tissue and circulation. This opens new avenues to explore whether selective inhibition of this protease could reduce cardiovascular risk and ameliorate metabolic status in obese subjects.

OBJECTIVE Growth of white adipose tissue takes place in normal development and in obesity. A pool of adipose progenitors is responsible for the formation of new adipocytes and for the potential of this tissue to expand in response to chronic energy overload. However, factors controlling self-renewal of human adipose progenitors are largely unknown. We investigated the expression profile and the role of activin A in this process. RESEARCH DESIGN AND METHODS Expression of INHBA/activin A was investigated in three types of human adipose progenitors. We then analyzed at the molecular level the function of activin A during human adipogenesis. We finally investigated the status of activin A in adipose tissues of lean and obese subjects and analyzed macrophage-induced regulation of its expression. RESULTS INHBA/activin A is expressed by adipose progenitors from various fat depots, and its expression dramatically decreases as progenitors differentiate into adipocytes. Activin A regulates the number of undifferentiated progenitors. Sustained activation or inhibition of the activin A pathway impairs or promotes, respectively, adipocyte differentiation via the C/EBPβ-LAP and Smad2 pathway in an autocrine/paracrine manner. Activin A is expressed at higher levels in adipose tissue of obese patients compared with the expression levels in lean subjects. Indeed, activin A levels in adipose progenitors are dramatically increased by factors secreted by macrophages derived from obese adipose tissue. CONCLUSIONS Altogether, our data show that activin A plays a significant role in human adipogenesis. We propose a model in which macrophages that are located in adipose tissue regulate adipose progenitor self-renewal through activin A.

Obesity is a state of chronic low-grade inflammation. Limiting white adipose tissue (WAT) expansion and therefore reducing inflammation could be effective in preventing the progression of obesity and the development of associated complications. We investigated the effects of 1,2-vinyldithiin (1,2-DT), a garlic-derived organosulfur, on the differentiation and inflammatory state of human preadipocytes. Preadipocytes were prepared from subcutaneous adipose tissue of nonobese young women and differentiated in the presence of 1,2-DT. Inflammatory preadipocytes were obtained following treatment with human macrophage-secreted factors. 1,2-DT (100 micromol/L) significantly reduced gene expression of PPARgamma2 (-40%), CCAAT/enhancer binding protein-alpha (-25%), lipoprotein lipase (-22%), leptin (-30%), and adiponectin (-15%). Lipid accumulation was also significantly diminished in preadipocytes differentiated in the presence of 100 micromol/L 1,2-DT (-37%) compared with controls. Furthermore, 100 micromol/L 1,2-DT treatment for 10 d significantly reduced PPARgamma activity (-27%). The protein expression of perilipin and the secretion levels for 2 adipokines, leptin and adiponectin, were significantly diminished in 1,2-DT-cultured preadipocytes (-37, -51, and -43%, respectively). Moreover, the secretion of inflammatory molecules (interleukin-6 and monocyte chemoattractant protein-1) induced by macrophage-secreted factors was partially abolished in 100 micromol/L 1,2-DT-treated preadipocytes (-28 and -25%, respectively). In conclusion, we demonstrated that 1,2-DT, a garlic-derived organosulfur, has antiadipogenic and antiinflammatory actions on human preadipocytes and may be a novel, antiobesity nutraceutical.