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Article: Bile Acids Induce Neurite Outgrowth in Nsc-34 Cells via TGR5 and a Distinct Transcriptional Profile.

Ackerman, Hayley D / Gerhard, Glenn S

2023 Volume 16, Issue 2

Abstract: Increasing evidence supports a neuroprotective role for bile acids in major neurodegenerative disorders. We studied major human bile acids as signaling molecules for their two cellular receptors, farnesoid X receptor (FXR or NR1H4) and G protein-coupled ... ...

Abstract	Increasing evidence supports a neuroprotective role for bile acids in major neurodegenerative disorders. We studied major human bile acids as signaling molecules for their two cellular receptors, farnesoid X receptor (FXR or NR1H4) and G protein-coupled bile acid receptor 1 (GPBAR1 or TGR5), as potential neurotrophic agents. Using quantitative image analysis, we found that 20 μM deoxycholic acid (DCA) could induce neurite outgrowth in NSC-34 cells that was comparable to the neurotrophic effects of the culture control 1 μM retinoic acid (RA), with lesser effects observed for chenodexoycholic acid (CDCA) at 20 μM, and similar though less robust neurite outgrowth in SH-SY5Y cells. Using chemical agonists and antagonists of FXR, LXR, and TGR5, we found that TGR5 agonism was comparable to DCA stimulation and stronger than RA, and that neither FXR nor liver X receptor (LXR) inhibition could block bile acid-induced neurite growth. RNA sequencing identified a core set of genes whose expression was regulated by DCA, CDCA, and RA. Our data suggest that bile acid signaling through TGR5 may be a targetable pathway to stimulate neurite outgrowth.
Language	English
Publishing date	2023-01-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16020174
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Article ; Online: Effects of dietary sugar restriction on hepatic fat in youth with obesity.

Distefano, Johanna K / Gerhard, Glenn S

Minerva pediatrics

2023

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children. Like adults, children can develop the progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), which is characterized by hepatic inflammation, often in the ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children. Like adults, children can develop the progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), which is characterized by hepatic inflammation, often in the presence of fibrosis. Children with NAFLD are at higher risk of liver-related complications, metabolic dysfunction, and cardiovascular disease in adulthood. Many factors contribute to the escalating prevalence of NAFLD in the pediatric population, among which are an array of dietary patterns such as overnutrition, poor diet quality, and heavy consumption of fat and sugar, including fructose. Findings from an increasing number of epidemiological studies support a connection between high habitual sugar consumption and NAFLD, especially within the context of obesity, but these studies are not able to demonstrate whether sugar is a contributing factor or instead an indicator of an overall poor diet (or lifestyle) quality. To date, only four randomized controlled dietary interventions assessing the effects of sucrose/fructose restriction on hepatic fat fraction in youth with obesity have been published. The objectives of this review are to summarize the key findings from these dietary interventions to achieve a better understanding of the strength of the relationship between dietary sugar restriction and liver fat reduction, despite their inherent limitations, and to discuss the potential impact of weight loss and fat mass reduction on improvement in hepatic steatosis.
Language	English
Publishing date	2023-06-07
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062664-X
ISSN	2724-5780
ISSN (online)	2724-5780
DOI	10.23736/S2724-5276.23.07209-9
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Article ; Online: Heme as a Taste Molecule.

Gerhard, Glenn S

Current nutrition reports

2020 Volume 9, Issue 3, Page(s) 290–295

Abstract: Purpose of review: The sense of taste has evolved to enable the identification of appropriate substances to consume, to acquire nutrients, and to avoid consuming potential toxins. Five basic taste classes have been recognized, although there may be ... ...

Abstract	Purpose of review: The sense of taste has evolved to enable the identification of appropriate substances to consume, to acquire nutrients, and to avoid consuming potential toxins. Five basic taste classes have been recognized, although there may be others, including metallic taste, which have not been well defined. The purpose of this review was to survey available data from diverse sources to determine how much was known about the molecular basis for metallic taste. Recent findings: Metallic taste has been studied in the context of dysgeusia, primarily using non-heme iron as an inducer of metallic taste sensation. However, recent efforts by industry to develop plant-based meat substitutes have suggested that iron in the form of heme may be the main molecule underlying the taste of meat. Little work has been done on heme as a taste molecule. Data support a primary role for heme in metallic taste that may have evolved as part of a means to consume and preserve elemental iron for physiological needs.
MeSH term(s)	Heme/chemistry ; Heme/pharmacology ; Humans ; Iron ; Taste/drug effects ; Taste/physiology ; Taste Perception/drug effects ; Taste Perception/physiology
Chemical Substances	Heme (42VZT0U6YR) ; Iron (E1UOL152H7)
Language	English
Publishing date	2020-06-22
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2161-3311
ISSN (online)	2161-3311
DOI	10.1007/s13668-020-00320-6
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Article ; Online: Ghosts and Munchkins: follow the medical student road?

Gerhard, Glenn S

The clinical teacher

2019 Volume 17, Issue 1, Page(s) 103–105

MeSH term(s)	Humans ; Students, Medical
Language	English
Publishing date	2019-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2151518-9
ISSN	1743-498X ; 1743-4971
ISSN (online)	1743-498X
ISSN	1743-4971
DOI	10.1111/tct.13009
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Article ; Online: Metabolic dysfunction and nonalcoholic fatty liver disease risk in individuals with a normal body mass index.

DiStefano, Johanna K / Gerhard, Glenn S

Current opinion in gastroenterology

2023 Volume 39, Issue 3, Page(s) 156–162

Abstract: Purpose of review: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but is also common in individuals with a normal body mass index (BMI), who also experience the hepatic inflammation, fibrosis, and decompensated cirrhosis ... ...

Abstract	Purpose of review: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but is also common in individuals with a normal body mass index (BMI), who also experience the hepatic inflammation, fibrosis, and decompensated cirrhosis associated with NAFLD progression. The clinical evaluation and treatment of NAFLD in this patient population are challenging for the gastroenterologist. A better understanding of the epidemiology, natural history, and outcomes of NAFLD in individuals with normal BMI is emerging. This review examines the relationship between metabolic dysfunction and clinical characteristics associated with NAFLD in normal-weight individuals. Recent findings: Despite a more favorable metabolic profile, normal-weight NAFLD patients exhibit metabolic dysfunction. Visceral adiposity may be a critical risk factor for NAFLD in normal-weight individuals, and waist circumference may be better than BMI for assessing metabolic risk in these patients. Although screening for NAFLD is not presently recommended, recent guidelines may assist clinicians in the diagnosis, staging, and management of NAFLD in individuals with a normal BMI. Summary: Individuals with a normal BMI likely develop NAFLD as a result of different etiologies. Subclinical metabolic dysfunction may be a key component of NAFLD in these patients, and efforts to better understand this relationship in this patient population are needed.
MeSH term(s)	Humans ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/epidemiology ; Non-alcoholic Fatty Liver Disease/diagnosis ; Body Mass Index ; Risk Factors ; Obesity/complications ; Obesity/epidemiology ; Liver Cirrhosis/etiology ; Liver Cirrhosis/complications
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	632571-3
ISSN	1531-7056 ; 0267-1379
ISSN (online)	1531-7056
ISSN	0267-1379
DOI	10.1097/MOG.0000000000000920
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Article ; Online: Just a Cut.

Gerhard, Glenn S

The New England journal of medicine

2017 Volume 376, Issue 5, Page(s) 500–501

Language	English
Publishing date	2017--02
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1615253
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Article: NAFLD in normal weight individuals.

DiStefano, Johanna K / Gerhard, Glenn S

Diabetology & metabolic syndrome

2022 Volume 14, Issue 1, Page(s) 45

Abstract: Nonalcoholic fatty liver disease (NAFLD) can develop in lean individuals. Despite a better metabolic profile, the risk of disease progression to hepatic inflammation, fibrosis, and decompensated cirrhosis in the lean is similar to that in obesity-related ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) can develop in lean individuals. Despite a better metabolic profile, the risk of disease progression to hepatic inflammation, fibrosis, and decompensated cirrhosis in the lean is similar to that in obesity-related NAFLD and lean individuals may experience more severe hepatic consequences and higher mortality relative to those with a higher body mass index (BMI). In the absence of early symptoms and abnormal laboratory findings, lean individuals are not likely to be screened for NAFLD or related comorbidities; however, given the progressive nature of the disease and the increased risk of morbidity and mortality, a clearer understanding of the natural history of NAFLD in lean individuals, as well as efforts to raise awareness of the potential health risks of NAFLD in lean individuals, are warranted. In this review, we summarize available data on NAFLD prevalence, clinical characteristics, outcomes, and mortality in lean individuals and discuss factors that may contribute to the development of NAFLD in this population, including links between dietary and genetic factors, menopausal status, and ethnicity. We also highlight the need for greater representation of lean individuals in NAFLD-related clinical trials, as well as more studies to better characterize lean NAFLD, develop improved screening algorithms, and determine specific treatment strategies based on underlying etiology.
Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2518786-7
ISSN	1758-5996
ISSN	1758-5996
DOI	10.1186/s13098-022-00814-z
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Article ; Online: Methods for Estimating Personal Disease Risk and Phylogenetic Diversity of Hematopoietic Stem Cells.

Craig, Jack M / Gerhard, Glenn S / Sharma, Sudip / Yankovskiy, Anastasia / Miura, Sayaka / Kumar, Sudhir

Molecular biology and evolution

2023 Volume 41, Issue 1

Abstract: An individual's chronological age does not always correspond to the health of different tissues in their body, especially in cases of disease. Therefore, estimating and contrasting the physiological age of tissues with an individual's chronological age ... ...

Abstract	An individual's chronological age does not always correspond to the health of different tissues in their body, especially in cases of disease. Therefore, estimating and contrasting the physiological age of tissues with an individual's chronological age may be a useful tool to diagnose disease and its progression. In this study, we present novel metrics to quantify the loss of phylogenetic diversity in hematopoietic stem cells (HSCs), which are precursors to most blood cell types and are associated with many blood-related diseases. These metrics showed an excellent correspondence with an age-related increase in blood cancer incidence, enabling a model to estimate the phylogeny-derived age (phyloAge) of HSCs present in an individual. The HSC phyloAge was generally older than the chronological age of patients suffering from myeloproliferative neoplasms (MPNs). We present a model that relates excess HSC aging with increased MPN risk. It predicted an over 200 times greater risk based on the HSC phylogenies of the youngest MPN patients analyzed. Our new metrics are designed to be robust to sampling biases and do not rely on prior knowledge of driver mutations or physiological assessments. Consequently, they complement conventional biomarker-based methods to estimate physiological age and disease risk.
MeSH term(s)	Humans ; Phylogeny ; Hematopoietic Stem Cells/metabolism ; Myeloproliferative Disorders/genetics ; Myeloproliferative Disorders/metabolism ; Aging ; Neoplasms
Language	English
Publishing date	2023-12-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msad279
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Article ; Online: Long Noncoding RNAs and Human Liver Disease.

DiStefano, Johanna K / Gerhard, Glenn S

Annual review of pathology

2021 Volume 17, Page(s) 1–21

Abstract: Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions ... ...

Abstract	Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease.
MeSH term(s)	Genome, Human ; Humans ; Non-alcoholic Fatty Liver Disease ; RNA, Long Noncoding/genetics
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2021-08-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2227429-7
ISSN	1553-4014 ; 1553-4006
ISSN (online)	1553-4014
ISSN	1553-4006
DOI	10.1146/annurev-pathol-042320-115255
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Article ; Online: Clinical significance of iron deficiency among candidates for metabolic surgery.

Benotti, Peter N / Wood, G Craig / Dove, James / Kaberi-Otarod, Jila / Still, Christopher D / Gerhard, Glenn S / Bistrian, Bruce R

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

2023 Volume 19, Issue 9, Page(s) 981–989

Abstract: Background: Iron deficiency (ID), a known complication after metabolic surgery, is common among preoperative patients in the presence of inflammation. Evidence is now accumulating that preoperative ID may adversely affect perioperative outcomes.: ... ...

Abstract	Background: Iron deficiency (ID), a known complication after metabolic surgery, is common among preoperative patients in the presence of inflammation. Evidence is now accumulating that preoperative ID may adversely affect perioperative outcomes. Objectives: To investigate the relationship between preoperative iron status and the risk of postoperative severe anemia. In addition, this study investigates the relationship between preoperative iron status and length of surgical stay SETTING: A large regional tertiary health system. Methods: Among patients who underwent metabolic surgery between 2004 and 2020, 5171 patients had a full iron nutritional assessment prior to surgery. Study patients were divided into multiple smaller groups (10 female groups and 7 male groups) on the basis of levels of serum ferritin and Transferrin Saturation (T Sat) < or ≥20%. Study patients were followed after surgery and the time to the development of severe anemia (hemoglobin < 8 gm/dL) was recorded. Hospital length of stay (LOS) was analyzed in relation to preoperative iron status. Results: Lower ferritin levels were associated with older age in males (P = .0001) and younger age in females (P < .0001). For males, after adjustment for age, body mass index (BMI), and year of surgery, surgical LOS was prolonged in those with T Sat <20% (P = .0041). For females the time until the development of severe anemia was associated with baseline iron status (P < .0001). Conclusions: Male preoperative patients for metabolic surgery with T Sat <20% are at risk for increased surgical LOS. Females with low ferritin levels consistent with ID are at increased risk for the development of postoperative severe anemia.
MeSH term(s)	Humans ; Male ; Female ; Clinical Relevance ; Iron Deficiencies ; Iron ; Bariatric Surgery ; Anemia ; Ferritins ; Anemia, Iron-Deficiency/complications
Chemical Substances	Iron (E1UOL152H7) ; Ferritins (9007-73-2)
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2274243-8
ISSN	1878-7533 ; 1550-7289
ISSN (online)	1878-7533
ISSN	1550-7289
DOI	10.1016/j.soard.2023.04.333
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