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The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry--based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a coregulator of FXR. FXR interacted with the nutrient-sensitive kinase AMPK in the cytoplasm of target cells and was phosphorylated in its hinge domain. In cultured human and murine hepatocytes and enterocytes, pharmacological activation of AMPK inhibited FXR transcriptional activity and prevented FXR coactivator recruitment to promoters of FXR-regulated genes. Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine. In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury. Together, our data indicate that AMPK directly phosphorylates and regulates FXR transcriptional activity to precipitate liver injury under conditions favoring cholestasis., Introduction In addition to their role as lipid emulsifiers, bile acids (BAs) are now also recognized as important regulators of cholesterol, bile acid, and triglyceride and glucose metabolism, as well [...]

Osteoporosis is a chronic and asymptomatic disease characterized by low bone mass and skeletal microarchitectural deterioration, increased risk of fracture, and associated comorbidities most prevalent in the elderly. Due to an increasingly aging population, osteoporosis has become a major health issue requiring innovative disease management. Proteins are important for bone by providing building blocks and by exerting specific regulatory function. This is why adequate protein intake plays a considerable role in both bone development and bone maintenance. More specifically, since an increase in the overall metabolism of collagen can lead to severe dysfunctions and a more fragile bone matrix and because orally administered collagen can be digested in the gut, cross the intestinal barrier, enter the circulation, and become available for metabolic processes in the target tissues, one may speculate that a collagen-enriched diet provides benefits for the skeleton. Collagen-derived products such as gelatin or hydrolyzed collagen (HC) are well acknowledged for their safety from a nutritional point of view; however, what is their impact on bone biology? In this manuscript, we critically review the evidence from literature for an effect of HC on bone tissues in order to determine whether HC may represent a relevant alternative in the design of future nutritional approaches to manage osteoporosis prevention. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion A healthy skin provides protection against intrinsic and extrinsic factors. Skin aging is characterized by structural and morphological alterations affecting skin health, integrity, and functionality, resulting in visible aging signs.The primary objective of this study was to assess the effect of a collagen peptide dietary supplement on skin aging in the East Asian population.Eighty‐five healthy women, aged from 43 to 65 years old, were randomly assigned to the collagen supplement (CP, 5 g) or placebo (maltodextrin, 5 g) group. To standardize daily skin care, the volunteers in both groups used a specific face cream for 28 days prior to and throughout the supplementation period, creating an equal baseline for the assessment of the efficacy of CP on several skin parameters. At baseline, day 28 and day 84, the following hallmarks of skin and nail aging were assessed: dermis density, skin moisture and elasticity, wrinkle visibility, beauty perception, and nail color.After 84 days, a significant improvement of dermis density and skin moisture was observed in the collagen peptides group compared to the placebo group. Positive effects on skin elasticity, wrinkle visibility, nail color, and overall beauty perception were already observed within 28 days of supplementation in the CP group, while the same effects in the placebo group were only observed after 84 days.Taken together, these results show that, in addition to a standardized skin care, daily supplementation with 5 g of collagen peptides positively affects visible signs of skin and nail aging in the East Asian population. [ABSTRACT FROM AUTHOR]

Background: Joint discomfort is a widespread and growing problem in active adults. The rising interest in preventative nutrition has increased the demand for supplements reducing joint discomfort. Protocols assessing the effect of a nutritional intervention on health commonly involve a series of face-to-face meetings between participants and study staff that can weigh on resources, participant availabilities, and even increase dropout rates. Digital tools are increasingly added to protocols to facilitate study conduct, but fully digitally run studies are still scarce. With the increasing interest in real-world studies, the development of health apps for mobile devices to monitor study outcomes is of great importance., Objective: The purpose of this real-world study was to develop a specific mobile app, Ingredients for Life, to conduct a 100% digital study testing the effectiveness of a hydrolyzed cartilage matrix (HCM) supplement on joint discomfort in a heterogeneous group of healthy, active consumers., Methods: The Ingredients for Life mobile app using a visual analog scale was specifically developed to monitor the variation in joint pain after exercise by the study participants. A total of 201 healthy and physically active women and men (18-72 years old) with joint pain completed the study over a period of 16 weeks. Participants were randomly allocated to the study groups and did not receive any dietary or lifestyle advice. Each participant indicated one area of joint pain and logged the type and duration of their weekly activities. They received blinded study supplements and took a daily regimen of 1 g of HCM (HCM group) or 1 g of maltodextrin (placebo group) for 12 weeks while weekly logging joint pain scores in the app. This was followed by a 4-week washout period during which participants continued reporting their joint pain scores (until the end of week 16)., Results: Joint pain was reduced within 3 weeks of taking a low dosage of HCM (1 g/day), regardless of gender, age group, and activity intensity when compared with the placebo group. After stopping supplementation, joint pain scores gradually increased but still remained significantly lower than those of the placebo group after 4 weeks of washout. The low dropout rate (<6% of participants, mainly in the placebo group) demonstrates that the digital study was well received by the study population., Conclusions: The digital tool allowed us to measure a heterogeneous group of active adults in a real-world setting (without any lifestyle intervention), thus promoting inclusivity and diversity. With low dropout rates, it demonstrates that mobile apps can generate qualitative, quantifiable, real-world data showcasing supplement effectiveness. The study confirmed that the oral intake of a low dose (1 g/day) of HCM led to a significant reduction of joint pain from 3 weeks after starting supplementation., (©Christie Newman, Els Adriaens, Nicolina Virgilio, Sara Vleminckx, Sara de Pelsmaeker, Janne Prawitt, Catarina I F Silva. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.04.2023.)

Background: The effect of dietary collagen on managing digestive symptoms is currently lacking in the literature., Objective: To gain a better understanding of this issue, we conducted a 2-phase mixed methods study., Methods: Phase 1 was a mixed methods design to explore current attitude and practice among consumers and health care practitioners. The findings were used to design an 8-week phase 2 digital study called Gutme! conducted in the United States in healthy female volunteers (BMI>25 kg/m 2 ). Our aim was, first, to determine the feasibility of conducting a fully digital mixed methods study; second, the study explored the effect of an 8-week daily supplementation of 20 g dietary collagen peptide (Peptan) on digestive symptoms. Phase 2 was a prospective, open-label, longitudinal, single-arm study. Participation involved 2 weeks of baseline tracking (digestive symptoms, mood, stool, and lifestyle) using an app, followed by 8 weeks of tracking and taking 20 g collagen peptide supplement split into 2 dosages per day. Participants were required to complete a web-based symptom questionnaire at baseline, week 2, and week 8, as well as participate in 2 scheduled video interviews., Results: Phase 1 revealed that consumer awareness of collagen for digestive health is low (64/204, 31.4%). Among the dietitians prescribing collagen for their patients, the most common dosage was 20 g a day with notable effects after 6 weeks of intake. Within the phase 2 study, of the 40 recruited participants, 14 (35%) completed the full course of supplementation. The findings indicate that 93% (13/14) of those who completed the study experienced a reduction in digestive symptoms, which included bloating., Conclusions: A mixed methods digital study design is feasible and acceptable for collecting relevant data in a real-life setting. The use of a 20 g daily collagen peptide supplement may reduce bloating and improve mild digestive symptoms in otherwise healthy female adults in the absence of any other dietary or lifestyle interventions., Trial Registration: ClinicalTrials.gov NCT04245254; https://clinicaltrials.gov/ct2/show/NCT04245254., (©Mariette Abrahams, Rochez O’Grady, Janne Prawitt. Originally published in JMIR Formative Research (https://formative.jmir.org), 31.05.2022.)

Atopic dermatitis (AD) is a chronic allergic dermatosis characterized by epidermal thickening and dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the chronic stage. Among chemokines and chemokine receptors associated with inflammation, increased levels of CX3CL1 (fractalkine) and its unique receptor, CX3CR1, have been observed in human AD. We have thus investigated their role and mechanism of action in experimental models of AD and psoriasis. AD pathology and immune responses, but not psoriasis, were profoundly decreased in CX3CR1-deficient mice and upon blocking CX3CL1-CX3CR1 interactions in wild-type mice. CX3CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX3CR1 expression by both Th2 and Th1 cells was required to induce AD. Surprisingly, unlike in allergic asthma, where CX3CL1 and CX3CR1 regulate the pathology by controlling effector CD4(+) T cell survival within inflamed tissues, adoptive transfer experiments established CX3CR1 as a key regulator of CD4(+) T cell retention in inflamed skin, indicating a new function for this chemokine receptor. Therefore, although CX3CR1 and CX3CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases., (© 2014 Staumont-Sallé et al.)

The bile acid receptor farnesoid X receptor (FXR) is expressed in adipose tissue, but its function remains poorly defined. Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipocyte differentiation and function. The aim of this study was to analyze the role of FXR in adipocyte function and to assess whether it modulates PPARγ action. Therefore, we tested the responsiveness of FXR-deficient mice (FXR(-/-)) and cells to the PPARγ activator rosiglitazone. Our results show that genetically obese FXR(-/-)/ob/ob mice displayed a resistance to rosiglitazone treatment. In vitro, rosiglitazone treatment did not induce normal adipocyte differentiation and lipid droplet formation in FXR(-/-) mouse embryonic fibroblasts (MEFs) and preadipocytes. Moreover, FXR(-/-) MEFs displayed both an increased lipolysis and a decreased de novo lipogenesis, resulting in reduced intracellular triglyceride content, even upon PPARγ activation. Retroviral-mediated FXR re-expression in FXR(-/-) MEFs restored the induction of adipogenic marker genes during rosiglitazone-forced adipocyte differentiation. The expression of Wnt/β-catenin pathway and target genes was increased in FXR(-/-) adipose tissue and MEFs. Moreover, the expression of several endogenous inhibitors of this pathway was decreased early during the adipocyte differentiation of FXR(-/-) MEFs. These findings demonstrate that FXR regulates adipocyte differentiation and function by regulating two counteracting pathways of adipocyte differentiation, the PPARγ and Wnt/β-catenin pathways.