Browsing by Subject "Fasting"

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Open Access
Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.
(PLoS One, 2012) Huffman, Kim M; Redman, Leanne M; Landerman, Lawrence R; Pieper, Carl F; Stevens, Robert D; Muehlbauer, Michael J; Wenner, Brett R; Bain, James R; Kraus, Virginia B; Newgard, Christopher B; Ravussin, Eric; Kraus, William E
OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)). METHODS: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test. RESULTS: Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both). CONCLUSIONS: Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I). TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151.
Open Access
Characterization of a canine model of glycogen storage disease type IIIa.
(Dis Model Mech, 2012-11) Yi, Haiqing; Thurberg, Beth L; Curtis, Sarah; Austin, Stephanie; Fyfe, John; Koeberl, Dwight D; Kishnani, Priya S; Sun, Baodong
Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.
Open Access
Leptin metabolically licenses T cells for activation to link nutrition and immunity.
(J Immunol, 2014-01-01) Saucillo, Donte C; Gerriets, Valerie A; Sheng, John; Rathmell, Jeffrey C; Maciver, Nancie J
Immune responses are highly energy-dependent processes. Activated T cells increase glucose uptake and aerobic glycolysis to survive and function. Malnutrition and starvation limit nutrients and are associated with immune deficiency and increased susceptibility to infection. Although it is clear that immunity is suppressed in times of nutrient stress, mechanisms that link systemic nutrition to T cell function are poorly understood. We show in this study that fasting leads to persistent defects in T cell activation and metabolism, as T cells from fasted animals had low glucose uptake and decreased ability to produce inflammatory cytokines, even when stimulated in nutrient-rich media. To explore the mechanism of this long-lasting T cell metabolic defect, we examined leptin, an adipokine reduced in fasting that regulates systemic metabolism and promotes effector T cell function. We show that leptin is essential for activated T cells to upregulate glucose uptake and metabolism. This effect was cell intrinsic and specific to activated effector T cells, as naive T cells and regulatory T cells did not require leptin for metabolic regulation. Importantly, either leptin addition to cultured T cells from fasted animals or leptin injections to fasting animals was sufficient to rescue both T cell metabolic and functional defects. Leptin-mediated metabolic regulation was critical, as transgenic expression of the glucose transporter Glut1 rescued cytokine production of T cells from fasted mice. Together, these data demonstrate that induction of T cell metabolism upon activation is dependent on systemic nutritional status, and leptin links adipocytes to metabolically license activated T cells in states of nutritional sufficiency.
Open Access
Prevalence and correlates of proteinuria in Kampala, Uganda: a cross-sectional pilot study.
(BMC Res Notes, 2016-02-16) Lunyera, Joseph; Stanifer, John W; Ingabire, Prossie; Etolu, Wilson; Bagasha, Peace; Egger, Joseph R; Patel, Uptal D; Mutungi, Gerald; Kalyesubula, Robert
BACKGROUND: Despite the increasing prevalence of chronic kidney disease (CKD) in sub-Saharan Africa, few community-based screenings have been conducted in Uganda. Opportunities to improve the management of CKD in sub-Saharan Africa are limited by low awareness, inadequate access, poor recognition, and delayed presentation for clinical care. Therefore, the Uganda Kidney Foundation engaged key stakeholders in performing a screening event on World Kidney Day. METHODS: We conducted a cross-sectional pilot study in March 2013 from a convenience sample of adult, urban residents in Kampala, Uganda. We advertised the event using radio and television announcements, newspapers, billboards, and notice boards at public places, such as places of worship. Subsequently, we screened for proteinuria, hypertension, fasting glucose impairment, and obesity in a central and easily-accessible location. RESULTS: We enrolled 141 adults most of whom were female (57 %), young (64 %; 18-39 years), and had a professional occupation (52 %). The prevalence of proteinuria (13 %; 95 % confidence interval [CI] 7-19 %), hypertension (38 %; 95 % CI 31-47 %), and impaired fasting glucose (13 %; 95 % CI 9-20 %) were high in this study population. Proteinuria was most prevalent among young (18-39 years) adults (n = 14; 16 %) and among those who reported a history of alcohol intake (n = 10; 32 %). CONCLUSIONS: The prevalence of proteinuria was high among a convenience sample of urban residents in a sub-Saharan African setting. These results represent an important effort by the Ugandan Kidney Foundation to increase awareness and recognition of CKD, and they will help formulate additional epidemiological studies on NCDs in Uganda which are urgently needed and now feasible.
Open Access
Prevalence, components, and correlates of metabolic syndrome (MetS) among elderly Muscovites.
(Arch Gerontol Geriatr, 2012-09) Metelskaya, Victoria A; Shkolnikova, Maria A; Shalnova, Svetlana A; Andreev, Evgeny M; Deev, Alexander D; Jdanov, Dmitri A; Shkolnikov, Vladimir M; Vaupel, James W
The goal of this study is to estimate the prevalence of MetS, together with its components and correlates, among elderly Russians. Our population-based sample included randomly selected residents of Moscow aged 55 and older: 955 women with an average age of 67.6, and 833 men with an average age of 68.9. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). The prevalence of MetS was found to be 41.7% in women and 26.8% in men. It tended to decrease with age in men, but not in women. MetS was inversely related to education in women, but not in men. The most prevalent individual components of MetS were as follows: hypertension (64.4%), abdominal obesity (55%), and decreased high density lipoprotein cholesterol (HDL C) (46%) for women; and hypertension (71%) and fasting hyperglycemia (35.2%) for men. An elevated level of triglycerides (TG) was the rarest MetS component, affecting 23.5% of women and 22.1% of men. The higher female prevalence of MetS was attributable to abdominal obesity. MetS was found to be associated with markers of insulin resistance (IR), low-grade inflammation, and insufficient fibrinolysis. Although the metabolic burden is an important contributor to high levels of ill-health and cardiovascular mortality among elderly Russians (especially women), it does not explain why cardiovascular mortality is much higher in Russia than in other industrialized countries.