Hereditary fructose intolerance, caused by mutations in the ALDOB gene, is an unusual cause of hypoglycemia. ALDOB encodes the enzyme aldolase B, responsible for the hydrolysis of fructose ...1-phosphate in the liver. Here, we report the case of a 33-year-old female patient who consulted due to repetitive episodes of weakness, dizziness and headache after food ingestion. An ambulatory 72-h continuous glucose monitoring revealed multiple short hypoglycemic episodes over the day. After biochemical exclusion of other endocrine causes of hypoglycemia, hereditary fructose intolerance seemed a plausible diagnosis. Repeated measurements of urinary fructose revealed pathologic fructosuria, but genetic testing for the three most common mutations in ALDOB resulted negative. We decided to perform complete Sanger sequencing of the ALDOB gene and encountered a variant consisting of a T>A substitution in position 1963 of the ALDOB transcript (c.1693T>A). This position is located within the 3′ untranslated region of exon 9, 515 nucleotides downstream the stop codon. After complete withdrawal of dietary fructose and sucrose, the patient presented no new hypoglycemic episodes.
Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to ...explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles.
We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices.
Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC).
In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.
The heterogeneity of the human intestinal epithelium has hindered the understanding of the pathophysiology of distinct specialized cell types on a single-cell basis in disease states. Described here ...is a workflow for the cryopreservation of endoscopically obtained human intestinal mucosal biopsies, subsequent preparation of this tissue to yield highly viable fluorescence-activated cell sorting (FACS)isolated human intestinal epithelial cell (IEC) single-cell suspensions compatible with successful library preparation and deep single-cell RNA sequencing (scRNAseq). We validated this protocol in deep scRNAseq of 59,653 intestinal cells in 10 human participants. Furthermore, primary intestinal cultures were successfully generated from cryopreserved tissue, capable of surviving in short-term culture and suitable for physiological assays studying gut peptide secretion from rare hormone-producing enteroendocrine cells in humans. This study offers an accessible avenue for single-cell transcriptomics and
studies from cryopreserved intestinal mucosal biopsies. These techniques may be used in the future to dissect and define novel aberrations to the intestinal ecosystem that lead to the development and progression of disease states in humans, even in rare IEC populations.
Background: Obesity is a complex disease characterized by dysregulation in energy intake. The reward circuitry of the central nervous system is essential in food intake regulation. However, the ...effects of a short- and long-term fast on reward activity and subsequent caloric intake are not well understood. Methods: The neuroimaging food paradigm consisted of three pseudo-continuous arterial spin labeling (pCASL) MRI scans during an ad libitum nutrient drink (Ensure®) test (NDT) (drinking until maximal fullness). The first scan was performed before starting the NDT (Hunger) after a >12-hr (long-term) overnight fast or a 4-hr (short-term fast) after a 380-kcal standard breakfast, the second scan after reaching maximal fullness (Satiation), and the third scan 30-min after satiation (Satiety). Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated from the pCASL data. Brain regions of interest (right and left caudate, putamen, and nucleus accumbens NAc) were segmented from T2 volumes using Freesurfer (run_first_all) and used to mask CBF maps to determine the average CBF in each region. Changes in CBF were used as a proxy of neural activity. Results: A total of 43 patients with obesity (mean±SD age 37±10 years, body-mass index BMI 35.1±4.4kg/m2, 72% females) completed the study, 29 in the long-term fast and 14 in the short-term fast group. The long-term fast group consumed 1306±125 kcal in the NDT compared with 1125±301 kcal in the short-term fast (p=0.1). The short-term fast group had a significantly lower activity (CBF) in the left and right NAc, and left and right caudate nucleus during hunger, satiation, and satiety, and in the left and right putamen only at hunger. Conclusions: Recent (<4hrs) caloric intake decreases reward neural activity but not ad libitum energy intake in patients with obesity.
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