Publications
348 results found
Goldstone AP, Miras AD, Scholtz S, et al., 2015, Link between increased satiety gut hormones and reduced food reward following gastric bypass surgery for obesity, Journal of Clinical Endocrinology & Metabolism, Vol: 101, Pages: 599-609, ISSN: 1945-7197
Context: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weightloss maintenance, reducing appetite, and also food reward, via unclear mechanisms.Objective: To investigate the role of elevated satiety gut hormones after RYGB, we examined foodhedonic-reward responses following their acute post-prandial suppression.Design: Randomised placebo-controlled double-blind cross-over experimental medicine studies.Patients: Two groups, over 5 months after RYGB for obesity (n7–11), compared with non-obesecontrols (n10), or patients after gastric banding (BAND) surgery (n9).Intervention: Studies were performed after acute administration of the somatostatin analogueOctreotide or saline. In one study, patients after RYGB, and non-obese controls, performed abehavioral progressive ratio task (PRT) for chocolate sweets. In another study, patients after RYGB,and controls after BAND surgery, performed a functional magnetic resonance imaging (fMRI) foodpicture evaluation task.Main outcome measures: Octreotide increased both appetitive food reward (breakpoint) in thePRT (n9), and food appeal (n9) and reward system blood oxygen level dependent (BOLD) signal(n7) in the fMRI task, in the RYGB group, but not in control groups.ISSN
Guess ND, Dornhorst A, Oliver N, et al., 2015, A randomized controlled trial: the effect of inulin on weight management and ectopic fat in subjects with prediabetes, Nutrition & Metabolism, Vol: 12, ISSN: 1743-7075
BackgroundFat infiltration of the liver, muscle and pancreas is associated with insulin resistance and risk of diabetes. Weight loss reduces ectopic fat deposition and risk of diabetes, but is difficult to sustain to due to compensatory increases in appetite. Fermentable carbohydrates have been shown to decrease appetite and food intake, and promote weight loss in overweight subjects. In animal studies, fermentable carbohydrate reduces ectopic fat independent of weight loss. We aimed to investigate the effect of the fermentable carbohydrate inulin on weight maintenance, appetite and ectopic fat in subjects with prediabetes.MethodsForty-four subjects with prediabetes were randomized to 18 weeks’ inulin or cellulose supplementation. During weeks 1–9 (weight loss phase) all subjects had four visits with a dietitian to guide them towards a 5 % weight loss. During weeks 10–18 (weight maintenance phase) subjects continued taking their assigned supplementation and were asked to maintain the weight they had lost but were offered no further support. All subjects attended study sessions at baseline, 9 and 18 weeks for measurement of weight; assessment of adipose tissue and ectopic fat content by magnetic resonance imaging and magnetic resonance spectroscopy; glucose, insulin and GLP-1 levels following a meal tolerance test; and appetite by ad libitum meal test and visual analogue scales.ResultsBoth groups lost approximately 5 % of their body weight by week nine (−5.3 ± 0.1 % vs −4.3 ± 0.4 %, p = 0.13, but the inulin group lost significantly more weight between 9 and 18 weeks (−2.3 ± 0.5 % vs −0.6 ± 0.4 %, p = 0.012). Subjects taking inulin had lower hepatic (p = 0.02) and soleus muscle (p < 0.05) fat content at 18 weeks compared to control even after controlling for weight loss and consumed les
Chambers ES, Viardot A, Psichas A, et al., 2015, Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults, Gut, Vol: 64, Pages: 1744-1754, ISSN: 0017-5749
Objective The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.Design To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.Results Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.
Gale C, Logan KM, Jeffries S, et al., 2015, Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy, International Journal of Obesity, Vol: 39, Pages: 629-632, ISSN: 1476-5497
Chambers E, Viardot A, Psichas A, et al., 2015, Effects of Elevating Colonic Propionate on Liver Fat Content in Adults with Non-Alcoholic Fatty Liver Disease, FASEB JOURNAL, Vol: 29, ISSN: 0892-6638
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- Citations: 1
Comninos AN, Anastasovska J, Sahuri-Arisoylu M, et al., 2015, Kisspeptin signaling in the amygdala modulates reproductive hormone secretion, Brain Structure & Function, Vol: 221, Pages: 2035-2047, ISSN: 1863-2661
Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its significance in other areas of the brain. KISS1 and its cognate receptor are expressed in the amygdala, a key limbic brain structure with inhibitory projections to hypothalamic centers involved in gonadotropin secretion. We therefore hypothesized that kisspeptin has effects on neuronal activation and reproductive pathways beyond the hypothalamus and particularly within the amygdala. To test this, we mapped brain neuronal activity (using manganese-enhanced MRI) associated with peripheral kisspeptin administration in rodents. We also investigated functional relevance by measuring the gonadotropin response to direct intra-medial amygdala (MeA) administration of kisspeptin and kisspeptin antagonist. Peripheral kisspeptin administration resulted in a marked decrease in signal intensity in the amygdala compared to vehicle alone. This was associated with an increase in luteinizing hormone (LH) secretion. In addition, intra-MeA administration of kisspeptin resulted in increased LH secretion, while blocking endogenous kisspeptin signaling within the amygdala by administering intra-MeA kisspeptin antagonist decreased both LH secretion and LH pulse frequency. We provide evidence for the first time that neuronal activity within the amygdala is decreased by peripheral kisspeptin administration and that kisspeptin signaling within the amygdala contributes to the modulation of gonadotropin release and pulsatility. Our data suggest that kisspeptin is a ‘master regulator’ of reproductive physiology, integrating limbic circuits with the regulation of gonadotropin-releasing hormone neurons and reproductive hormone secretion.
Sam AH, Sleeth ML, Thomas EL, et al., 2015, Circulating pancreatic polypeptide concentrations predict visceral and liver fat content, Journal of Clinical Endocrinology and Metabolism, Vol: 100, Pages: 1048-1052, ISSN: 0021-972X
Context and objective:No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat.Patients and Methods:Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy.Results:Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01).Conclusions:Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.
Thomas EL, Bell JD, 2015, Body Fat MRS, EMAGRES, Vol: 4, Pages: 663-671, ISSN: 2055-6101
Cuthbertson DJ, Weickert MO, Lythgoe D, et al., 2014, External validation of the fatty liver index and lipid accumulation product indices, using <SUP>1</SUP>H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals, EUROPEAN JOURNAL OF ENDOCRINOLOGY, Vol: 171, Pages: 561-569, ISSN: 0804-4643
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- Citations: 112
Gale C, Thomas EL, Jeffries S, et al., 2014, Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study (vol 99, pg 1034, 2014), AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 100, Pages: 1213-1213, ISSN: 0002-9165
Thomas EL, Bell J, 2014, Body fat: our own Janus, Physiology News, Pages: 24-27
Nunn AVW, Guy GW, Bell JD, 2014, The intelligence paradox; will ET get the metabolic syndrome? Lessons from and for Earth, NUTRITION & METABOLISM, Vol: 11
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- Citations: 12
Goldstone AP, Prechtl CG, Scholtz S, et al., 2014, Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 99, Pages: 1319-1330, ISSN: 0002-9165
Scholtz S, Miras AD, Chhina N, et al., 2014, Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding, Gut, Vol: 63, Pages: 891-902, ISSN: 0017-5749
Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations.Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity.Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients.Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour.
Scholtz S, Miras AD, Chhina N, et al., 2014, Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding, GUT, Vol: 63, Pages: 891-902, ISSN: 0017-5749
Koivula RW, Heggie A, Barnett A, et al., 2014, Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium, DIABETOLOGIA, Vol: 57, Pages: 1132-1142, ISSN: 0012-186X
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- Citations: 26
Miras AD, Scholtz S, Chhina N, et al., 2014, Role for Increased Plasma PYY and GLP-1 in Reducing Anticipatory Food Reward after Gastric Bypass Surgery, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Comninos AN, Anastasovska J, Sahuri-Arisoylu M, et al., 2014, Kisspeptin Inhibits Neuronal Activity in the Amygdala of Male Mice, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Daud NM, Ismail NA, Thomas EL, et al., 2014, The Impact of Oligofructose on Stimulation of Gut Hormones, Appetite Regulation and Adiposity, OBESITY, Vol: 22, Pages: 1430-1438, ISSN: 1930-7381
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- Citations: 60
Gale C, Thomas EL, Jeffries S, et al., 2014, Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study, American Journal of Clinical Nutrition, Vol: 99, Pages: 1034-1040, ISSN: 0002-9165
Background: The effect of mode of infant feeding on adiposity deposition is not fully understood.Objective: The objective was to test the hypothesis that differences in total and regional adipose tissue content and intrahepatocellular lipid (IHCL) arise in early infancy between breast- and formula-fed infants and to describe longitudinal changes.Design: This prospective longitudinal cohort study was performed in 2 hospitals in the United Kingdom. Healthy, full-term, appropriate weight-for-gestational age infants were recruited; adipose tissue volume and distribution were directly quantified by using whole-body magnetic resonance imaging; IHCL was assessed by in vivo proton magnetic resonance spectroscopy. Measurements were performed after birth (median age: 13 d) and at 6–12 wk of age. Method of infant feeding was recorded prospectively by using maternally completed feeding diaries. Breastfed was defined as >80% of feeds consisting of breast milk at both points; formula-fed was defined as >80% of feeds consisting of formula milk at both points.Results: Longitudinal results were obtained from 70 infants (36 breastfed, 9 mixed-fed, and 25 formula-fed). No differences were found in total or regional adipose tissue or IHCL between breastfed and formula-fed infants. In pooled analyses including all feeding groups, IHCL and total adipose tissue approximately doubled between birth and 6–12 wk: IHCL after birth (median: 0.949; IQR: 0.521–1.711) and at 6–12 wk (1.828; 1.376–2.697; P < 0.001) and total adipose tissue after birth (0.749 L; 0.620–0.928 L) and at 6–12 wk (1.547 L; 1.332–1.790 L; P < 0.001). Increasing adiposity was characterized by greater relative increases in subcutaneous than in internal adipose tissue depots.Conclusions: No differences were detectable in adipose tissue or IHCL accretion between breastfed and formula-fed infants up to 2 mo. The substantial increase in IHCL seen over this period in bo
Frost G, Sleeth ML, Sahuri-Arisoylu M, et al., 2014, The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism, Nature Communications, Vol: 5, Pages: 1-11, ISSN: 2041-1723
Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.
Bodinham CL, Smith L, Thomas EL, et al., 2014, Efficacy of increased resistant starch consumption in human type 2 diabetes, Endocrine Connections, Vol: 3, Pages: 75-84, ISSN: 2049-3614
Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.
Sung S, Holmes H, Wainwright L, et al., 2014, Multimetallic Complexes and Functionalized Gold Nanoparticles Based on a Combination of d- and f-Elements, INORGANIC CHEMISTRY, Vol: 53, Pages: 1989-2005, ISSN: 0020-1669
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- Citations: 30
Smith L, Thomas EL, Bell JD, et al., 2014, The association between objectively measured sitting and standing with body composition: a pilot study using MRI, BMJ OPEN, Vol: 4, ISSN: 2044-6055
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- Citations: 25
Vasu V, Durighel G, Thomas L, et al., 2014, Preterm nutritional intake and MRI phenotype at term age: a prospective observational study, BMJ OPEN, Vol: 4, ISSN: 2044-6055
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- Citations: 24
Anstee QM, Knapp S, Maguire EP, et al., 2013, Mutations in the <i>Gabrb1</i> gene promote alcohol consumption through increased tonic inhibition, NATURE COMMUNICATIONS, Vol: 4, ISSN: 2041-1723
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- Citations: 40
Thomas EL, Fitzpatrick JA, Frost G, et al., 2013, Metabolic Syndrome, Overweight and Fatty Liver, Handbook of Nutrition and Food, 3rd Edition., Editors: Heber
Forbes S, Godsland IF, Taylor-Robinson SD, et al., 2013, A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid, DIABETOLOGIA, Vol: 56, Pages: 2021-2033, ISSN: 0012-186X
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- Citations: 19
Thomas EL, Fitzpatrick JA, Malik SJ, et al., 2013, Whole body fat: Content and distribution, PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY, Vol: 73, Pages: 56-80, ISSN: 0079-6565
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- Citations: 83
Vasu V, Thomas EL, Durighel G, et al., 2013, Early nutritional determinants of intrahepatocellular lipid deposition in preterm infants at term age, INTERNATIONAL JOURNAL OF OBESITY, Vol: 37, Pages: 500-504, ISSN: 0307-0565
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- Citations: 12
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