Examining the impacts of public transit on healthy aging through a natural experiment: study protocols and lessons learned from the Active El Paso project.

This paper describes protocols and experiences from a seven-year natural-experiment study in El Paso, Texas, a border city of predominantly Latino/Hispanic population. The study focuses on how Bus Rapid Transit (BRT) impacts physical activity and thus plays a role in alleviating obesity and related chronic diseases that impact healthy aging. Our protocols describe a longitudinal and case-comparison study, which compared residents exposed to new BRT stations with those who were not. This paper also introduces lessons and experiences to overcome the following challenges: delays in the BRT opening (the main intervention), the COVID-19 pandemic, methodological challenges, participant recruitment and retention, and predatory survey takers. Our transdisciplinary approach was pivotal in addressing these challenges. We also proposed and tested multi-level intervention strategies to reduce modifiable barriers to transit use. Our most important takeaway for researchers, practitioners, and policy makers is the importance of being flexible and ready to adapt to new circumstances. Future natural-experiment researchers need to become more versatile in an increasingly volatile and uncertain world.

Barriers and facilitators of physical activity among Latina immigrant and Mexican mothers living in the US and Mexico: A qualitative study.

Latina immigrant women are among the least physically active when compared with women in other racial/ethnic groups in the US. Similarly, Mexican mothers in Mexico have low rates of physical activity. Motherhood and immigration experiences are recognized barriers to engage in physical activity among Latina immigrant mothers. Less is known about the factors that promote and limit physical activity engagement among Mexican mothers in Mexico, and how their experiences compare with their immigrant counterparts. This transnational qualitative study aimed to investigate the barriers and facilitators of physical activity of 25 Latina mothers in Mexico and the US. Low-income Mexican mothers of kindergarten aged children and Latino mothers of similar aged children were recruited in San Luis Potosí, Mexico and central Illinois, US. Semi-structured interviews were administered by two bilingual and bicultural researchers in participants language of preference. Interviews were transcribed verbatim and analyzed using a thematic network approach and multi-stage coding analysis guided by the Socio-Ecological Model framework. We found that at the macro-level: 1) familial obligations, and 2) cold weather after migrating; at the mezzo-level: 1) changes in walking patterns, and 2) social cohesion (e.g., lack of an invitation to engage in activities); and at the micro-level: 1) individual perceptions, particularly unattainable perceptions of physical activity and 2) shift exhaustion were perceived as barriers and occasionally facilitators of physical activity by mothers in both countries. Context-specific interventions are needed to increase women's physical activity levels in the US and Mexico.

Essential role of systemic iron mobilization and redistribution for adaptive thermogenesis through HIF2-α/hepcidin axis.

Iron is an essential biometal, but is toxic if it exists in excess. Therefore, iron content is tightly regulated at cellular and systemic levels to meet metabolic demands but to avoid toxicity. We have recently reported that adaptive thermogenesis, a critical metabolic pathway to maintain whole-body energy homeostasis, is an iron-demanding process for rapid biogenesis of mitochondria. However, little information is available on iron mobilization from storage sites to thermogenic fat. This study aimed to determine the iron-regulatory network that underlies beige adipogenesis. We hypothesized that thermogenic stimulus initiates the signaling interplay between adipocyte iron demands and systemic iron liberation, resulting in iron redistribution into beige fat. To test this hypothesis, we induced reversible activation of beige adipogenesis in C57BL/6 mice by administering a ß3-adrenoreceptor agonist CL 316,243 (CL). Our results revealed that CL stimulation induced the iron-regulatory protein-mediated iron import into adipocytes, suppressed hepcidin transcription, and mobilized iron from the spleen. Mechanistically, CL stimulation induced an acute activation of hypoxia-inducible factor 2-α (HIF2-α), erythropoietin production, and splenic erythroid maturation, leading to hepcidin suppression. Disruption of systemic iron homeostasis by pharmacological HIF2-α inhibitor PT2385 or exogenous administration of hepcidin-25 significantly impaired beige fat development. Our findings suggest that securing iron availability via coordinated interplay between renal hypoxia and hepcidin down-regulation is a fundamental mechanism to activate adaptive thermogenesis. It also provides an insight into the effects of adaptive thermogenesis on systemic iron mobilization and redistribution.

Red Raspberry Polyphenols Attenuate High-Fat Diet-Driven Activation of NLRP3 Inflammasome and its Paracrine Suppression of Adipogenesis via Histone Modifications.

SCOPE: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors. METHODS AND RESULTS: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1ß reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1ß-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells. CONCLUSIONS: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction.

α-Linolenic acid-enriched butter attenuated high fat diet-induced insulin resistance and inflammation by promoting bioconversion of n-3 PUFA and subsequent oxylipin formation.

α-Linolenic acid (ALA) is an essential fatty acid and the precursor for long-chain n-3 PUFA. However, biosynthesis of n-3 PUFA is limited in a Western diet likely due to an overabundance of n-6 PUFA. We hypothesized that dietary reduction of n-6/n-3 PUFA ratio is sufficient to promote the biosynthesis of long-chain n-3 PUFA, leading to an attenuation of high fat (HF) diet-induced obesity and inflammation. C57BL/6 J mice were fed a HF diet from ALA-enriched butter (n3Bu, n-6/n-3=1) in comparison with isocaloric HF diets from either conventional butter lacking both ALA and LA (Bu, n-6/n-3=6), or margarine containing a similar amount of ALA and abundant LA (Ma, n-6/n-3=6). Targeted lipidomic analyses revealed that n3Bu feeding promoted the bioconversion of long-chain n-3 PUFA and their oxygenated metabolites (oxylipins) derived from ALA and EPA. The n3Bu supplementation attenuated hepatic TG accumulation and adipose tissue inflammation, resulting in improved insulin sensitivity. Decreased inflammation by n3Bu feeding was attributed to the suppression of NF-κB activation and M1 macrophage polarization. Collectively, our work suggests that dietary reduction of the n-6/n-3 PUFA ratio, as well as total n-3 PUFA consumed, is a crucial determinant that facilitates n-3 PUFA biosynthesis and subsequent lipidomic modifications, thereby conferring metabolic benefits against obesity-induced inflammation and insulin resistance.

Synthesis of benziporphyrins and heterobenziporphyrins and an assessment of the diatropic characteristics of the protonated species.

Benzitripyrranes were prepared by reacting diphenyl-substituted benzenedicarbinols with excess pyrrole in the presence of BF3·Et2O. These dipyrrolic compounds underwent acid-catalyzed condensations with a pyrrole dialdehyde to afford good yields of diphenylbenziporphyrins, and further reaction with palladium(II) acetate gave stable organometallic derivatives. The X-ray crystal structure of a palladium(II) benziporphyrin showed that the system deviates significantly from planarity. Although the benzitripyrranes failed to give stable macrocyclic products with furan or thiophene dialdehydes, they afforded tetraphenyl heterobenziporphyrins upon reaction with diphenyl-substituted furan- or thiophenedicarbinols and BF3·Et2O. Benziporphyrins and their heteroanalogues showed no indication of a diamagnetic ring current by proton NMR spectroscopy, but addition of TFA gave rise to the formation of weakly diatropic dications.