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Metabolomics and Lipidomics Analysis of the NIA CALERIE Trial
Author(s) -
Kristal Bruce S,
Gathungu Rose M,
Bird Susan S,
Marur Vasant R,
Sniatynski Matthew J,
Sheldon Diane P
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.42.7
Subject(s) - lipidomics , metabolomics , caloric theory , calorie restriction , post hoc analysis , medicine , randomized controlled trial , calorie , clinical trial , physiology , bioinformatics , biology
Calorie Restriction (CR) is the most potent, robust, and reproducible known means of extending longevity and decreasing morbidity in a vast range of animal species short of primates. Despite 80 years of research, the relevance of this observation for humans remains unknown. Relevance is supported by the established link between obesity and morbidity in humans, and the health status of individuals voluntarily participating in a caloric restricted lifestyle. Other potential linkages are being directly studied in the NIA/NIH‐sponsored CALERIE ( C omprehensive A ssessment of L ong‐term E ffects of R educing I ntake of E nergy) clinical trial. CALERIE enrolled 238 individuals and collected blood samples at 6 time points over 24 months. We previously examined metabolomics (via HPLC separation with coulometric electrode array‐based detection) and lipidomics (via high resolution LC‐MS‐based lipidomics) effects of the CALERIE intervention and compared these data to those previously obtained in studies of ad libitum fed and calorically restricted FBFN1 rats (males/females, different ages and extents and durations of CR). The results were, surprisingly, nearly completely negative. Retrospective Post‐Hoc analyses identified three potential reasons for these negative findings. First the original trial and our analyses intended to strictly follow trial design (i.e., intention to treat analysis), were powered for a 25% drop in caloric intake – a larger and more consistent goal than was obtained. Second, many individuals on the low calorie diet intervention lost weight in year one but gained in year two – a shift in caloric balance for which our analyses initially were, again in accordance with an intent‐to‐treat design, unprepared to compensate. Third, and most important, we determined that exposure of the forearm to high temperatures prior to some phlebotomy (termed “hot‐box”) time points — which was essential to assess one listed secondary clinical outcome of the trial — destroyed self‐similarity for our measures, rendering the baseline sample unusable for our standard normalization and control methods. Correcting for this revealed some of the expected biological/biochemical differences and provided a potentially interesting signal related to altered stress response in relationship to some aspect of caloric intake, obesity, and/or energy expenditure, consistent with the cognate literature in animal models of normal and delayed aging. We will discuss the results, the implication for metabolomics and lipidomics studies, and initial, promising re‐analysis of these CALERIE data. Support or Funding Information NIA/NIH