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"Pickering, Richard T"
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Vitamin D3, 25-Hydroxyvitamin D3, and 1,25-Dihydroxyvitamin D3 Uptake in Cultured Human Mature Adipocytes
2025
Background/Objectives: Vitamin D3 is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D3 and 1,25(OH)2D3, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Methods: Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D3 and 1,25(OH)2D3 or the combination of vitamin D3, 25(OH)D3 and 1,25(OH)2D3. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D3 release under basal and isoproterenol-stimulated conditions using 3H-vitamin D3 and scintillation counting. Results: Vitamin D3 uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D3 and 1,25(OH)2D3 peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D3 release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Conclusions: Adipocytes selectively retain vitamin D3 while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies—particularly in individuals with excess adiposity—may improve bioavailability and metabolic efficacy.
Journal Article
Dietary Cholesterol Intake Is Not Associated with Risk of Type 2 Diabetes in the Framingham Offspring Study
by
Singer, Martha
,
Bradlee, M.
,
Moore, Lynn
in
Adult
,
Biomarkers - blood
,
Blood Glucose - metabolism
2018
Identification of diet and lifestyle risk factors for prevention of type 2 diabetes mellitus (T2DM) is of great importance. The specific role of dietary cholesterol (DC) in T2DM risk is unclear. This study uses data from 2192 Framingham Offspring Study subjects to estimate the effects of DC alone and in combination with markers of a healthy diet and other lifestyle factors on fasting glucose and risk of T2DM or impaired fasting glucose (IFG) over 20 years of follow-up. Dietary data were derived from two sets of three-day food records. Statistical methods included mixed linear regression and Cox proportional hazard’s modeling to adjust for confounding. There were no statistically significant differences in glucose levels over 20 years of follow-up across DC intake categories (<200, 200–<300, and ≥300 mg/day) and no increased risk of T2DM/IFG associated with higher intakes. The HR for T2DM/IFG associated with consumption of ≥300 mg/day of DC was 0.87 (95% CI: 0.68–1.10). In contrast, subjects with lower intakes of fish, whole grains, and fiber had higher T2DM/IFG risk. DC consumption was not associated with fasting glucose levels or risk of T2DM/IFG over 20 years of follow-up.
Journal Article
Dietary Cholesterol, Lipid Levels, and Cardiovascular Risk among Adults with Diabetes or Impaired Fasting Glucose in the Framingham Offspring Study
by
Bradlee, M. Loring
,
Singer, Martha R.
,
Mott, Melanie M.
in
adults
,
blood lipids
,
cardiovascular diseases
2018
Previous recommendations to limit dietary cholesterol intake have been eliminated for most adults. Questions remain about whether dietary cholesterol has adverse cardiovascular effects among individuals with impaired fasting glucose or diabetes (IFG/T2DM). We used data for 993 adults (40.9% female), ages 35–<65 years, with prevalent IFG/T2DM in the prospective Framingham Offspring Study to address this question. Dietary cholesterol was assessed using 3-day diet records at exams 3 and 5 and used to classify subjects into sex-specific tertiles of mean cholesterol intake. Outcomes included fasting lipid levels over 20 years and incident cardiovascular disease (CVD). Statistical analyses included repeated measures mixed regression models and Cox proportional hazards models to adjust for confounding. Among adults with T2DM/IFG, there was no consistent association between dietary cholesterol intake and fasting low-density lipoprotein (LDL), high-density lipoprotein (HDL), LDL/HDL ratio, or triglycerides over 20 years of follow-up. In longitudinal analyses, the adjusted hazard ratio for CVD in the highest (vs. lowest) sex-specific tertile of cholesterol intake was 0.61 (95% CI: 0.41, 0.90). These analyses provide no evidence of an adverse association between dietary cholesterol and serum lipid levels or atherosclerotic CVD risk among adults with prevalent IFG/T2DM.
Journal Article
Vitamin Dsub.3, 25-Hydroxyvitamin Dsub.3, and 1,25-Dihydroxyvitamin Dsub.3 Uptake in Cultured Human Mature Adipocytes
by
Holick, Michael F
,
Pickering, Richard. T
,
Soriano, José Miguel
in
Adipose tissues
,
Alfacalcidol
,
Calcifediol
2025
Background/Objectives: Vitamin D[sub.3] is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D[sub.3] and 1,25(OH)[sub.2]D[sub.3], remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Methods: Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D[sub.3] and 1,25(OH)[sub.2]D[sub.3] or the combination of vitamin D[sub.3], 25(OH)D[sub.3] and 1,25(OH)[sub.2]D[sub.3]. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D[sub.3] release under basal and isoproterenol-stimulated conditions using [sup.3]H-vitamin D[sub.3] and scintillation counting. Results: Vitamin D[sub.3] uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D[sub.3] and 1,25(OH)[sub.2]D[sub.3] peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D[sub.3] release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Conclusions: Adipocytes selectively retain vitamin D[sub.3] while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies—particularly in individuals with excess adiposity—may improve bioavailability and metabolic efficacy.
Journal Article
Vitamin D 3 , 25-Hydroxyvitamin D 3 , and 1,25-Dihydroxyvitamin D 3 Uptake in Cultured Human Mature Adipocytes
by
Pickering, Richard T
,
Holick, Michael F
,
Soriano, José Miguel
in
Adipocytes - drug effects
,
Adipocytes - metabolism
,
Calcifediol - metabolism
2025
Vitamin D
is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D
and 1,25(OH)
D
, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes.
Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D
and 1,25(OH)
D
or the combination of vitamin D
, 25(OH)D
and 1,25(OH)
D
. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D
release under basal and isoproterenol-stimulated conditions using
H-vitamin D
and scintillation counting.
Vitamin D
uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D
and 1,25(OH)
D
peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D
release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation.
Adipocytes selectively retain vitamin D
while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies-particularly in individuals with excess adiposity-may improve bioavailability and metabolic efficacy.
Journal Article
Deep marine systems : processes, deposits, environments, tectonics and sedimentation
2016,2015
Deep-water (below wave base) processes, although generally hidden from view, shape the sedimentary record of more than 65% of the Earth's surface, including large parts of ancient mountain belts. This book aims to inform advanced-level undergraduate and postgraduate students, and professional Earth scientists with interests in physical oceanography and hydrocarbon exploration and production, about many of the important physical aspects of deep-water (mainly deep-marine) systems. The authors consider transport and deposition in the deep sea, trace-fossil assemblages, and facies stacking patterns as an archive of the underlying controls on deposit architecture (e.g., seismicity, climate change, autocyclicity). Topics include modern and ancient deep-water sedimentary environments, tectonic settings, and how basinal and extra-basinal processes generate the typical characteristics of basin slopes, submarine canyons, contourite mounds and drifts, submarine fans, basin floors and abyssal plains.
Collagen Extraction from Animal Skin
by
Chisti, Yusuf
,
Matinong, Andrea Marie E.
,
Haverkamp, Richard G.
in
Amino acids
,
Animal skins
,
animals
2022
Collagen is the most abundant structural protein in animals. It is the major component of skin. It finds uses in cosmetics, medicine, yarn production and packaging. This paper reviews the extraction of collagen from hides of most consumed animals for meat with the focus on literature published since 2000. The different pretreatment and extraction techniques that have been investigated for producing collagen from animal skins are reviewed. Pretreatment by enzymatic, acid or alkaline methods have been used. Extraction by chemical hydrolysis, salt solubilization, enzymatic hydrolysis, ultrasound assisted extraction and other methods are described. Post-extraction purification methods are also explained. This compilation will be useful for anyone wishing to use collagen as a resource and wanting to further improve the extraction and purification methods.
Journal Article
Evaluation of the added value of Brain Natriuretic Peptide to a validated mortality risk-prediction model in older people using a standardised international clinical assessment tool
by
Pickering, John W.
,
Troughton, Richard
,
Jamieson, Hamish A.
in
Aged
,
Aged patients
,
Aged, 80 and over
2022
The ability to accurately predict the one-year survival of older adults is challenging for clinicians as they endeavour to provide the most appropriate care. Standardised clinical needs assessments are routine in many countries and some enable application of mortality prediction models. The added value of blood biomarkers to these models is largely unknown. We undertook a proof of concept study to assess if adding biomarkers to needs assessments is of value. Assessment of the incremental value of a blood biomarker, Brain Naturetic Peptide (BNP), to a one year mortality risk prediction model, RiskOP, previously developed from data from the international interRAI-HomeCare (interRAI-HC) needs assessment. Participants were aged ≥65 years and had completed an interRAI-HC assessment between 1 January 2013 and 21 August 2021 in Canterbury, New Zealand. Inclusion criteria was a BNP test within 90 days of the date of interRAI-HC assessment. The primary outcome was one-year mortality. Incremental value was assessed by change in Area Under the Receiver Operating Characteristic Curve (AUC) and Brier Skill, and the calibration of the final model. Of 14,713 individuals with an interRAI-HC assessment 1,537 had a BNP within 90 days preceding the assessment and all data necessary for RiskOP. 553 (36.0%) died within 1-year. The mean age was 82.6 years. Adding BNP improved the overall AUC by 0.015 (95% CI:0.004 to 0.028) and improved predictability by 1.9% (0.26% to 3.4%). In those with no Congestive Heart Failure the improvements were 0.029 (0.004 to 0.057) and 4.0% (0.68% to 7.6%). Adding a biomarker to a risk model based on standardised needs assessment of older people improved prediction of 1-year mortality. BNP added value to a risk prediction model based on the interRAI-HC assessment in those patients without a diagnosis of congestive heart failure.
Journal Article
Sediment delivery to sustain the Ganges-Brahmaputra delta under climate change and anthropogenic impacts
by
Akhter, Syed Humayun
,
Goodbred, Steven L.
,
Pickering, Jennifer L.
in
704/106/694/2739
,
704/172/4081
,
704/2151/215
2023
The principal nature-based solution for offsetting relative sea-level rise in the Ganges-Brahmaputra delta is the unabated delivery, dispersal, and deposition of the rivers’ ~1 billion-tonne annual sediment load. Recent hydrological transport modeling suggests that strengthening monsoon precipitation in the 21st century could increase this sediment delivery 34-60%; yet other studies demonstrate that sediment could decline 15-80% if planned dams and river diversions are fully implemented. We validate these modeled ranges by developing a comprehensive field-based sediment budget that quantifies the supply of Ganges-Brahmaputra river sediment under varying Holocene climate conditions. Our data reveal natural responses in sediment supply comparable to previously modeled results and suggest that increased sediment delivery may be capable of offsetting accelerated sea-level rise. This prospect for a naturally sustained Ganges-Brahmaputra delta presents possibilities beyond the dystopian future often posed for this system, but the implementation of currently proposed dams and diversions would preclude such opportunities.
The potential for enhanced sediment delivery to the Ganges-Brahmaputra delta exists, but it alone is insufficient to sustain the system. The delta may be resilient to climate change, but only in the absence of dam construction and water diversions.
Journal Article