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Stephanie M Wolahan, Mayumi L Prins, David L McArthur, Courtney R Real, David A Hovda, Neil A Martin, Paul M Vespa, Thomas C Glenn
BACKGROUND: The objective was to investigate the impact of targeting tight glycemic control (4.4-6.1 mM) on endogenous ketogenesis in severely head-injured adults. METHODS: The data were prospectively collected during a randomized, within-patient crossover study comparing tight to loose glycemic control, defined as 6.7-8.3 mM. Blood was collected periodically during both tight and loose glycemic control epochs. Post hoc analysis of insulin dose and total nutritional provision was performed...
October 19, 2016: Neurocritical Care
Kristina Hofmann, Christian Lamberz, Kira Piotrowitz, Nina Offermann, Diana But, Anja Scheller, Ashraf Al-Amoudi, Lars Kuerschner
Although the brain controls all main metabolic pathways in the whole organism, its lipid metabolism is partially separated from the rest of the body. Circulating lipids and other metabolites are taken up into brain areas like the hypothalamus and are locally metabolized and sensed involving several hypothalamic cell types. In this study we show that saturated and unsaturated fatty acids are differentially processed in the murine hypothalamus. The observed differences involve both lipid distribution and metabolism...
October 11, 2016: Glia
Gahl Levy, Naomi Habib, Maria Angela Guzzardi, Daniel Kitsberg, David Bomze, Elishai Ezra, Basak E Uygun, Korkut Uygun, Martin Trippler, Joerg F Schlaak, Oren Shibolet, Ella H Sklan, Merav Cohen, Joerg Timm, Nir Friedman, Yaakov Nahmias
Viruses lack the basic machinery needed to replicate and therefore must hijack the host's metabolism to propagate. Virus-induced metabolic changes have yet to be systematically studied in the context of host transcriptional regulation, and such studies shoul offer insight into host-pathogen metabolic interplay. In this work we identified hepatitis C virus (HCV)-responsive regulators by coupling system-wide metabolic-flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We found HCV-induced upregulation of glycolysis, ketogenesis and drug metabolism, with glycolysis controlled by activation of HNF4α, ketogenesis by PPARα and FXR, and drug metabolism by PXR...
October 10, 2016: Nature Chemical Biology
C E Geisler, C Hepler, M R Higgins, B J Renquist
BACKGROUND: The increased incidence of obesity and associated metabolic diseases has driven research focused on genetically or pharmacologically alleviating metabolic dysfunction. These studies employ a range of fasting-refeeding models including 4-24 h fasts, "overnight" fasts, or meal feeding. Still, we lack literature that describes the physiologically relevant adaptations that accompany changes in the duration of fasting and re-feeding. Since the liver is central to whole body metabolic homeostasis, we investigated the timing of the fast-induced shift toward glycogenolysis, gluconeogenesis, and ketogenesis and the meal-induced switch toward glycogenesis and away from ketogenesis...
2016: Nutrition & Metabolism
Emma O'Shea, Sinéad M Waters, Kate Keogh, Alan K Kelly, David A Kenny
BACKGROUND: The objective of this study was to investigate the effect of dietary restriction and subsequent compensatory growth on the relative expression of genes involved in volatile fatty acid transport, metabolism and cell proliferation in ruminal epithelial tissue of beef cattle. Sixty Holstein Friesian bulls (mean liveweight 370 ± 35 kg; mean age 479 ± 15 d) were assigned to one of two groups: (i) restricted feed allowance (RES; n = 30) for 125 d (Period 1) followed by ad libitum access to feed for 55 d (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n = 30)...
2016: Journal of Animal Science and Biotechnology
Ivan Kruljac, Miroslav Ćaćić, Petra Ćaćić, Vedran Ostojić, Mario Štefanović, Aljoša Šikić, Milan Vrkljan
Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department...
September 3, 2016: Endocrine
Weimin Wang, Chong Li, Fadi Li, Xiaojuan Wang, Xiaoxue Zhang, Ting Liu, Fang Nian, Xiangpeng Yue, Fei Li, Xiangyu Pan, Yongfu La, Futao Mo, Fangbin Wang, Baosheng Li
Early consumption of starter feed promotes rumen development in lambs. We examined rumen development in lambs fed starter feed for 5 weeks using histological and biochemical analyses and by performing high-throughput sequencing in rumen tissues. Additionally, rumen contents of starter feed-fed lambs were compared to those of breast milk-fed controls. Our physiological and biochemical findings revealed that early starter consumption facilitated rumen development, changed the pattern of ruminal fermentation, and increased the amylase and carboxymethylcellulase activities of rumen micro-organisms...
2016: Scientific Reports
Tristan Chalvon-Demersay, Patrick C Even, Daniel Tomé, Catherine Chaumontet, Julien Piedcoq, Claire Gaudichon, Dalila Azzout-Marniche
Fibroblast growth factor 21 (FGF21) is a polypeptide secreted by the liver and involved in several metabolic processes such as thermogenesis and lipid oxidation. The nutritional mechanisms controlling FGF21 production are poorly understood. This study aimed to investigate how dietary carbohydrates and proteins impact FGF21 production and how in turn, FGF21 is involved in the metabolic adaptation to changes in the carbohydrate and protein contents of the diet. For that purpose, we fed 25 male C57BL/6 mice diets composed of different protein and carbohydrate contents (normal-protein and carbohydrate diet (N=9, NPNC), low-protein high-carbohydrate diet (N=8, LPHC), high-protein low-carbohydrate diet (N=8, HPLC) for 3 weeks...
October 2016: Journal of Nutritional Biochemistry
Ming-Wei Chao, Chin-Hua Yang, Po-Ting Lin, Yu-Hsiu Yang, Yu-Chen Chuang, Meng-Chi Chung, Chia-Yi Tseng
PM2.5 travels along the respiratory tract and enters systemic blood circulation. Studies have shown that PM2.5 increases the incidence of various diseases not only in adults but also in newborn infants. It causes chronic inflammation in pregnant women and retards fetal development. In this study, pregnant rats were exposed to PM2.5 for extended periods of time and it was found that PM2.5 exposure increased immune cells in mother rats. In addition, cytokines and free radicals rapidly accumulated in the amniotic fluid and indirectly affected the fetuses...
August 19, 2016: Environmental Toxicology
Eva-Lena Stenblom, Emil Egecioglu, Caroline Montelius, Deepti Ramachandran, Britta Bonn, Björn Weström, Abdelhak Mansouri, Wolfgang Langhans, Charlotte Erlanson-Albertsson
Thylakoids reduce body weight gain and body fat accumulation in rodents. This study investigated whether an enhanced oxidation of dietary fat-derived fatty acids in the intestine contributes to the thylakoid effects. Male Sprague-Dawley rats were fed a high-fat diet with (n = 8) or without thylakoids (n = 8) for 2 wk. Body weight, food intake, and body fat were measured, and intestinal mucosa was collected and analyzed. Quantitative real-time PCR was used to measure gene expression levels of key enzymes involved in fatty acid transport, fatty acid oxidation, and ketogenesis...
September 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Kyung Eun Kim, Youngae Jung, Soonki Min, Miso Nam, Rok Won Heo, Byeong Tak Jeon, Dae Hyun Song, Chin-Ok Yi, Eun Ae Jeong, Hwajin Kim, Jeonghyun Kim, Seon-Yong Jeong, Woori Kwak, Do Hyun Ryu, Tamas L Horvath, Gu Seob Roh, Geum-Sook Hwang
Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice...
2016: Scientific Reports
Abdelilah Arredouani, Matteo Stocchero, Nicola Culeddu, Julia El-Sayed Moustafa, Jean Tichet, Beverley Balkau, Thierry Brousseau, Marco Manca, Mario Falchi
Low serum salivary amylase levels have been associated with a range of metabolic abnormalities, including obesity and insulin resistance. We recently suggested that low copy-number at the AMY1 gene, associated with lower enzyme levels, also increases susceptibility to obesity. To advance our understanding of the effect of AMY1 copy-number variation on metabolism, we compared the metabolomic signatures of high and low copy-number carriers. We analysed, using mass spectrometry and NMR, the sera of healthy normal-weight women carrying either low (LA:≤4 copies; n=50) or high (HA:≥8 copies; n=50) AMY1 copies...
July 19, 2016: Diabetes
Yudai Nonaka, Tetsuo Takagi, Makoto Inai, Shuhei Nishimura, Shogo Urashima, Kazumitsu Honda, Toshiaki Aoyama, Shin Terada
Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration...
August 1, 2016: Journal of Oleo Science
Yao Yan, Zong-Bao Wang, Chao-Ke Tang
PPAR-alpha expressed primarily in liver is essential for metabolic adaptation to starvation by inducing genes for beta-oxidation and ketogenesis to increase the utility of LCFAs and fibroblast growth factor 21. PPAR-delta induces genes for LCFA oxidation during fasting and endurance exercise in skeletal muscle. PPAR-delta also regulates glucose metabolism and mitochondrial biogenesis by inducing FOXO1 and PGC1-alpha. PPAR-gamma can induces the pathways to store LCFAs as triglycerides in adipocytes. Adiponectin, another important target of PPAR-gamma may maintain insulin sensitivity between adipocytes...
February 2016: Sheng Li Ke Xue Jin Zhan [Progress in Physiology]
R Paul Wadwa, H Peter Chase, Dan Raghinaru, Bruce A Buckingham, Irene Hramiak, David M Maahs, Laurel Messer, Trang Ly, Tandy Aye, Paula Clinton, Craig Kollman, Roy W Beck, John Lum
OBJECTIVE: To compare the frequency of elevated morning blood ketone levels according to age in 4-14 year olds with type 1 diabetes following overnight use of an automated low glucose insulin suspension system, or following control nights when the system was not used. RESEARCH DESIGN AND METHODS: For 28 children ages 4-9 years and 54 youth ages 10-14 years, elevation of morning blood ketone levels was assessed using the Precision Xtra Ketone meter following 1155 and 2345 nights, respectively...
July 12, 2016: Pediatric Diabetes
Younghoon Go, Ji Yun Jeong, Nam Ho Jeoung, Jae-Han Jeon, Bo-Yoon Park, Hyeon-Ji Kang, Chae-Myeong Ha, Young-Keun Choi, Sun Joo Lee, Hye Jin Ham, Byung-Gyu Kim, Keun-Gyu Park, So Young Park, Chul-Ho Lee, Cheol Soo Choi, Tae-Sik Park, W N Paul Lee, Robert A Harris, In-Kyu Lee
Hepatic steatosis is associated with increased insulin resistance and tricarboxylic acid (TCA) cycle flux, but decreased ketogenesis and pyruvate dehydrogenase complex (PDC) flux. This study examined whether hepatic PDC activation by inhibition of pyruvate dehydrogenase kinase 2 (PDK2) ameliorates these metabolic abnormalities. Wild-type mice fed a high-fat diet exhibited hepatic steatosis, insulin resistance, and increased levels of pyruvate, TCA cycle intermediates, and malonyl-CoA but reduced ketogenesis and PDC activity due to PDK2 induction...
October 2016: Diabetes
Blanka Kucejova, Joao Duarte, Santhosh Satapati, Xiaorong Fu, Olga Ilkayeva, Christopher B Newgard, James Brugarolas, Shawn C Burgess
Dysregulated mitochondrial metabolism during hepatic insulin resistance may contribute to pathophysiologies ranging from elevated glucose production to hepatocellular oxidative stress and inflammation. Given that obesity impairs insulin action but paradoxically activates mTORC1, we tested whether insulin action and mammalian target of rapamycin complex 1 (mTORC1) contribute to altered in vivo hepatic mitochondrial metabolism. Loss of hepatic insulin action for 2 weeks caused increased gluconeogenesis, mitochondrial anaplerosis, tricarboxylic acid (TCA) cycle oxidation, and ketogenesis...
July 12, 2016: Cell Reports
Anjeza Erickson, Régis Moreau
Fibroblast growth factor 21 (FGF21) gene expression is altered by a wide array of physiological, metabolic, and environmental factors. Among dietary factors, high dextrose, low protein, methionine restriction, short-chain fatty acids (butyric acid and lipoic acid), and all-trans-retinoic acid were repeatedly shown to induce FGF21 expression and circulating levels. These effects are usually more pronounced in liver or isolated hepatocytes than in adipose tissue or isolated fat cells. Although peroxisome proliferator-activated receptor α (PPARα) is a key mediator of hepatic FGF21 expression and function, including the regulation of gluconeogenesis, ketogenesis, torpor, and growth inhibition, there is increasing evidence of PPARα-independent transactivation of the FGF21 gene by dietary molecules...
June 10, 2016: Hormone Molecular Biology and Clinical Investigation
Marie Hennebelle, Alexandre Courchesne-Loyer, Valérie St-Pierre, Camille Vandenberghe, Christian-Alexandre Castellano, Mélanie Fortier, Daniel Tessier, Stephen C Cunnane
OBJECTIVES: The aim of the present study was to compare the effects of an α-linolenic acid-rich supplement (ALA-RS) on the ketogenic response and plasma long-chain ω-3 polyunsaturated fatty acid in healthy young adults and older individuals. METHODS: Ten young (25 ± 0.9 y) and 10 older adults (73.1 ± 2.2 y) consumed a flaxseed oil supplement providing 2 g/d of ALA for 4 wk. Plasma ketones, nonesterified fatty acids (NEFA), triacylglycerols, glucose, and insulin were measured over 6 h, before and after supplementation...
November 2016: Nutrition
Domenico Ciavardelli, Fabrizio Piras, Ada Consalvo, Claudia Rossi, Mirco Zucchelli, Carmine Di Ilio, Valerio Frazzini, Carlo Caltagirone, Gianfranco Spalletta, Stefano L Sensi
Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD...
July 2016: Neurobiology of Aging
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