Publications by authors named "Matthew P Gillum"

Article Synopsis
  • - The study examined gallbladder emptying and GLP-1 hormone responses in women with gestational diabetes mellitus (GDM) during pregnancy and postpartum to understand GDM's impact on these processes.
  • - Twenty women (15 with GDM and 15 with normal glucose tolerance) participated in mixed meal tests, revealing no differences in gallbladder emptying or GLP-1 responses between the two groups during pregnancy or after.
  • - Results showed that while gallbladder volume and emptying increased significantly during pregnancy, GLP-1 responses decreased, indicating that changes in gallbladder function may not be the main factors contributing to reduced GLP-1 levels in women with GDM.
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Objectives: Experimental and genetic studies suggest that fibroblast growth factor 21 (FGF21) modulates macronutrient and alcohol preferences, but evidence of such regulation in humans remains scarce. To address this gap in translation, we aimed to map the relationships between plasma FGF21 levels, FGF21 genetic variation and habitual macronutrient intake in a large human population.

Methods: We fine-mapped and performed colocalization of the FGF21 genetic region in GWAS summary statistics of plasma FGF21 levels and macronutrient intake.

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Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity.

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Background: Alcohol use disorder (AUD) affects 5% of the global population. Despite its high prevalence, the pathophysiology of AUD remains enigmatic, hindering the development of novel therapeutics. Interestingly, the liver hormone fibroblast growth factor 21 (FGF21), which is currently in late-stage clinical trials for the treatment of non-alcoholic steatohepatitis, has been implicated by recent genome-wide association studies as a regulator of alcohol consumption.

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In Greenland, traditional marine foods are increasingly being replaced by sucrose- and starch-rich foods. A knock-out c.273_274delAG variant in the sucrase-isomaltase () gene is relatively common in Greenland, with homozygous carriers being unable to digest sucrose and some starch.

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Depletion of gut microbiota is associated with inefficient energy extraction and reduced production of short-chain fatty acids from dietary fibers, which regulates colonic proglucagon (Gcg) expression and small intestinal transit in mice. However, the mechanism by which the gut microbiota influences dietary protein metabolism and its corresponding effect on the host physiology is poorly understood. Enteropeptidase inhibitors block host protein digestion and reduce body weight gain in diet-induced obese rats and mice, and therefore they constitute a new class of drugs for targeting metabolic diseases.

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Biological mechanisms to promote dietary balance remain unclear. Fibroblast growth factor 21 (FGF21) has been suggested to contribute to such potential regulation considering that FGF21 ) is genetically associated with carbohydrate/sugar and protein intake in opposite directions, ) is secreted after sugar ingestion and protein restriction, and ) pharmacologically reduces sugar and increases protein intake in rodents. To gain insight of the nature of this potential regulation, we aimed to study macronutrient interactions in the secretory regulation of FGF21 in healthy humans.

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p-cresol is a metabolite produced by microbial metabolism of aromatic amino acid tyrosine. p-cresol and its conjugated forms, p-cresyl sulfate and p-cresyl glucuronide, are uremic toxins that correlate positively with chronic kidney disease and diabetes pathogenesis. However, how p-cresol affects gut hormones is unclear.

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The gut microbiota impacts systemic levels of multiple metabolites including NAD precursors through diverse pathways. Nicotinamide riboside (NR) is an NAD precursor capable of regulating mammalian cellular metabolism. Some bacterial families express the NR-specific transporter, PnuC.

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N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans.

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Fibroblast growth factor 21 (FGF21) plays a key role in hepatic lipid metabolism and long-acting FGF21 analogs have emerged as promising drug candidates for the treatment of nonalcoholic steatohepatitis (NASH). It remains to characterize this drug class in translational animal models that recapitulate the etiology and hallmarks of human disease. To this end, we evaluated the long-acting FGF21 analog PF-05231023 in the GAN (Gubra Amylin NASH) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH.

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Aim: Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment.

Materials And Methods: In a double-blind, 12-week trial, 52 participants [50% male, age 47.

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BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.MethodsIn a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy.

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Aim: To evaluate the effect of curcumin treatment on hepatic fat content in obese individuals.

Materials And Methods: In a double-blind, parallel-group trial, 37 obese, non-diabetic individuals were randomized to placebo or curcumin treatment for 6 weeks. Curcumin was dosed as lecithin-formulated tablet; 200 mg twice daily.

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Aim/hypothesis: Urocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved.

Methods: We studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats.

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Background: Fibroblast growth factor 21 (FGF21) treatment improves metabolic homeostasis in diverse species, including humans. Physiologically, plasma FGF21 levels increase modestly after glucose ingestion, but it is unclear whether this is mediated by glucose itself or due to a secondary effect of postprandial endocrine responses. A refined understanding of the mechanisms that control FGF21 release in humans may accelerate the development of small-molecule FGF21 secretagogues to treat metabolic disease.

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Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms.

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Background & Aims: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced.

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The liver-derived hormone fibroblast growth factor 21 (FGF21) has recently been linked to preference for sweet-tasting food. We hypothesized, that surgery-induced changes in FGF21 could mediate the reduction in sweet food intake and preference following bariatric surgery. Forty participants (35 females) with severe obesity (BMI ≥ 35 kg/m) scheduled for roux-en-y gastric bypass ( = 30) or sleeve gastrectomy ( = 10) were included.

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Nicotinamide phosphoribosyltransferase (NAMPT) converts nicotinamide to NAD. As low hepatic NAD levels have been linked to the development of nonalcoholic fatty liver disease, we hypothesized that ablation of hepatic Nampt would affect susceptibility to liver injury in response to diet-induced metabolic stress. Following 3 weeks on a low-methionine and choline-free 60% high-fat diet, hepatocyte-specific Nampt knockout (HNKO) mice accumulated less triglyceride than WT littermates but had increased histological scores for liver inflammation, necrosis, and fibrosis.

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Background: Despite a consistent link between obesity and increased circulating levels of fibroblast growth factor-21 (FGF21), the effect of weight-loss interventions on FGF21 is not clear. We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21.

Method: Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks.

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Aims/hypothesis: Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males.

Methods: Fourteen festival participants (FP) were studied before, during and after 1 week's participation in Roskilde Festival.

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Omega-3 fatty acids from fish oil reduce triglyceride levels in mammals, yet the mechanisms underlying this effect have not been fully clarified, despite the clinical use of omega-3 ethyl esters to treat severe hypertriglyceridemia and reduce cardiovascular disease risk in humans. Here, we identified in bile a class of hypotriglyceridemic omega-3 fatty acid-derived N-acyl taurines (NATs) that, after dietary omega-3 fatty acid supplementation, increased to concentrations similar to those of steroidal bile acids. The biliary docosahexaenoic acid-containing (DHA-containing) NAT C22:6 NAT was increased in human and mouse plasma after dietary omega-3 fatty acid supplementation and potently inhibited intestinal triacylglycerol hydrolysis and lipid absorption.

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Scope: Brown and brite adipocytes within the mammalian adipose organ provide non-shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3-series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial.

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Objective: Glucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of amino acids are regulated by glucagon-dependent mechanism(s), while amino acids stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying the cycle and the possible impact of hepatic steatosis are unclear.

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