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Article: An interview with Philip McTernan, section editor for the basic science section.

McTernan, Philip G

2014 Volume 1, Page(s) 3

Abstract: Philip McTernan is a Reader Associate Professor within Warwick Medical School at the University ...

Abstract	Philip McTernan is a Reader Associate Professor within Warwick Medical School at the University of Warwick. His main interests involve understanding the causes and underlying mechanisms of obesity mediated type 2 diabetes and investigating potential therapeutic targets. He is currently researching the origins of inflammation in human adipocytes and is the Section Editor for the new 'Basic Science' section in BMC Obesity. In this interview we find out a little more about the key issues in this area of obesity research.
Language	English
Publishing date	2014-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2758687-X
ISSN	2052-9538
ISSN	2052-9538
DOI	10.1186/2052-9538-1-3
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Article: Endotoxemia, vitamin D and premature biological ageing in Arab adults with different metabolic states.

Al-Daghri, Nasser M / Sabico, Shaun / Ansari, Mohammed G A / Abdi, Saba / Tripathi, Gyanendra / Chrousos, George P / McTernan, Philip G

Saudi journal of biological sciences

2022 Volume 29, Issue 6, Page(s) 103276

Abstract: There are limited studies on the association of endotoxin, a potent mediator of gut-derived inflammation and telomere length (TL). We investigated (1) the influence of adiposity on endotoxin and TL amongst Saudi adults according to type 2 diabetes ... ...

Abstract	There are limited studies on the association of endotoxin, a potent mediator of gut-derived inflammation and telomere length (TL). We investigated (1) the influence of adiposity on endotoxin and TL amongst Saudi adults according to type 2 diabetes mellitus (T2DM) status and (2) the influence vitamin D may have on TL attrition. Anthropometric data and fasting blood samples were taken from 775 Saudi adults visiting different primary care centers in Riyadh [387 T2DM and 388 non-T2DM]. TL, derived from peripheral blood mononuclear cells, was analyzed by Quantitative real-time polymerase chain reaction and circulating endotoxin levels by Limulus Amebocyte Lysate assay. Subjects were stratified based on obesity and T2DM status. A significant lower TL was observed in the non-obese T2DM group as compared with their non-obese, non-T2DM counterparts (p = 0.002). Significant inverse associations between TL, endotoxin and endotoxin activity were observed in the cohort with obesity. Regression analysis showed that endotoxin was a significant predictor for TL in all subjects and even after stratification according to subgroups; with variances perceived in circulating TL stronger among non-T2DM obese (10%; p = 0.003) than non-T2DM non-obese (12%; p = 0.007). Also, in the non-T2DM group, TL and HDL-cholesterol predicted 29% of the variances perceived in 25(OH)D (p < 0.001). Taken together these findings show that circulating endotoxin and 25(OH)D are associated with premature biological ageing influenced by adiposity and metabolic state; suggesting future intervention studies to manipulate gut microbiome and or vitamin D levels may offer ways to mitigate premature TL attrition.
Language	English
Publishing date	2022-03-31
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	2515206-3
ISSN	2213-7106 ; 1319-562X
ISSN (online)	2213-7106
ISSN	1319-562X
DOI	10.1016/j.sjbs.2022.03.026
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Article ; Online: The impact of metabolic endotoxaemia on the browning process in human adipocytes.

Omran, Farah / Murphy, Alice M / Younis, Awais Z / Kyrou, Ioannis / Vrbikova, Jana / Hainer, Vojtech / Sramkova, Petra / Fried, Martin / Ball, Graham / Tripathi, Gyanendra / Kumar, Sudhesh / McTernan, Philip G / Christian, Mark

BMC medicine

2023 Volume 21, Issue 1, Page(s) 154

Abstract: Background: Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing ... ...

Abstract	Background: Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing changes in adipocyte mitochondrial function and reducing the proportion of BRITE (brown-in-white) adipocytes. Therefore, the present study investigated whether endotoxin (lipopolysaccharide; LPS) directly contributes to impaired human adipocyte mitochondrial function and browning in human adipocytes, and the relevant impact of obesity status pre and post bariatric surgery. Methods: Human differentiated abdominal subcutaneous (AbdSc) adipocytes from participants with obesity and normal-weight participants were treated with endotoxin to assess in vitro changes in mitochondrial function and BRITE phenotype. Ex vivo human AbdSc AT from different groups of participants (normal-weight, obesity, pre- and 6 months post-bariatric surgery) were assessed for similar analyses including circulating endotoxin levels. Results: Ex vivo AT analysis (lean & obese, weight loss post-bariatric surgery) identified that systemic endotoxin negatively correlated with BAT gene expression (p < 0.05). In vitro endotoxin treatment of AbdSc adipocytes (lean & obese) reduced mitochondrial dynamics (74.6% reduction; p < 0.0001), biogenesis (81.2% reduction; p < 0.0001) and the BRITE phenotype (93.8% reduction; p < 0.0001). Lean AbdSc adipocytes were more responsive to adrenergic signalling than obese AbdSc adipocytes; although endotoxin mitigated this response (92.6% reduction; p < 0.0001). Conclusions: Taken together, these data suggest that systemic gut-derived endotoxaemia contributes to both individual adipocyte dysfunction and reduced browning capacity of the adipocyte cell population, exacerbating metabolic consequences. As bariatric surgery reduces endotoxin levels and is associated with improving adipocyte functionality, this may provide further evidence regarding the metabolic benefits of such surgical interventions.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2 ; Endotoxemia/metabolism ; Adipocytes/metabolism ; Obesity/metabolism ; Lipopolysaccharides ; Endotoxins/metabolism
Chemical Substances	Lipopolysaccharides ; Endotoxins
Language	English
Publishing date	2023-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-023-02857-z
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Article ; Online: Tunicamycin-Induced Endoplasmic Reticulum Stress Mediates Mitochondrial Dysfunction in Human Adipocytes.

Jackisch, Laura / Murphy, Alice M / Kumar, Sudhesh / Randeva, Harpal / Tripathi, Gyanendra / McTernan, Philip G

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 9

Abstract: Context: Dysfunctional endoplasmic reticulum (ER) and mitochondria are known to contribute to the pathology of metabolic disease. This damage may occur, in part, as a consequence of ER-mitochondria cross-talk in conditions of nutrient excess such as ... ...

Abstract	Context: Dysfunctional endoplasmic reticulum (ER) and mitochondria are known to contribute to the pathology of metabolic disease. This damage may occur, in part, as a consequence of ER-mitochondria cross-talk in conditions of nutrient excess such as obesity. To date, insight into this dynamic relationship has not been characterized in adipose tissue. Therefore, this study investigated whether ER stress contributes to the development of mitochondrial inefficiency in human adipocytes from lean and obese participants. Methods: Human differentiated adipocytes from Chub-S7 cell line and primary abdominal subcutaneous adipocytes from lean and obese participants were treated with tunicamycin to induce ER stress. Key parameters of mitochondrial function were assessed, including mitochondrial respiration, membrane potential (MMP), and dynamics. Results: ER stress led to increased respiratory capacity in a model adipocyte system (Chub-S7 adipocytes) in a concentration and time dependent manner (24 h: 23%↑; 48 h: 68%↑, P < 0.001; 72 h: 136%↑, P < 0.001). This corresponded with mitochondrial inefficiency and diminished MMP, highlighting the formation of dysfunctional mitochondria. Morphological analysis revealed reorganization of mitochondrial network, specifically mitochondrial fragmentation. Furthermore, p-DRP1, a key protein in fission, significantly increased (P < 0.001). Additionally, adipocytes from obese subjects displayed lower basal respiration (49%↓, P < 0.01) and were unresponsive to tunicamycin in contrast to their lean counterparts, demonstrating inefficient mitochondrial oxidative capacity. Conclusion: These human data suggest that adipocyte mitochondrial inefficiency is driven by ER stress and exacerbated in obesity. Nutrient excess-induced ER stress leads to mitochondrial dysfunction that may therefore shift lipid deposition ectopically and thus have further implications on the development of related metabolic disorders.
MeSH term(s)	Adipocytes/drug effects ; Adipocytes/metabolism ; Adipocytes/pathology ; Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Adult ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; Cells, Cultured ; Cohort Studies ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/physiology ; Female ; Humans ; Mitochondria/drug effects ; Mitochondria/physiology ; Obesity/genetics ; Obesity/metabolism ; Obesity/pathology ; Tunicamycin/pharmacology ; Young Adult
Chemical Substances	Tunicamycin (11089-65-9)
Language	English
Publishing date	2020-05-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa258
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Article ; Online: Asthma and obesity: endotoxin another insult to add to injury?

Lad, Nikita / Murphy, Alice M / Parenti, Cristina / Nelson, Carl P / Williams, Neil C / Sharpe, Graham R / McTernan, Philip G

Clinical science (London, England : 1979)

2021 Volume 135, Issue 24, Page(s) 2729–2748

Abstract: Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on ...

Abstract	Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.
MeSH term(s)	Adipokines ; Asthma/etiology ; Asthma/physiopathology ; Diet/adverse effects ; Endotoxins ; Gastrointestinal Microbiome ; Humans ; Inflammation/physiopathology ; Obesity
Chemical Substances	Adipokines ; Endotoxins
Language	English
Publishing date	2021-12-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20210790
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Article ; Online: Vitamin D Levels as an Important Predictor for Type 2 Diabetes Mellitus and Weight Regain Post-Sleeve Gastrectomy.

Aladel, Alanoud / Murphy, Alice M / Abraham, Jenny / Shah, Neha / Barber, Thomas M / Ball, Graham / Menon, Vinod / Piya, Milan K / McTernan, Philip G

Nutrients

2022 Volume 14, Issue 10

Abstract: Weight Loss Surgery (WLS), including sleeve-gastrectomy (SG), results in significant weight loss and improved metabolic health in severe obesity (BMI ≥ 35 kg/m2). Previous studies suggest post-operative health benefits are impacted by nutrient ... ...

Abstract	Weight Loss Surgery (WLS), including sleeve-gastrectomy (SG), results in significant weight loss and improved metabolic health in severe obesity (BMI ≥ 35 kg/m2). Previous studies suggest post-operative health benefits are impacted by nutrient deficiencies, such as Vitamin D (25(OH)D) deficiency, while it is currently unknown whether nutrient levels may actually predict post-surgery outcomes. As such, this study investigated whether 25(OH)D levels could predict metabolic improvements in patients who underwent SG. Patients with severe obesity (n = 309; 75% female) undergoing SG participated in this ethics-approved, non-randomized retrospective cohort study. Anthropometry, clinical data, 25(OH)D levels and serum markers were collected at baseline, 6-, 12- and 18-months post-surgery. SG surgery resulted in significant improvements in metabolic health at 6- and 12-months post-surgery compared with baseline, as expected. Patients with higher baseline 25(OH)D had significantly lower HbA1c levels post-surgery (p < 0.01) and better post-surgical T2DM outcomes, including reduced weight regain (p < 0.05). Further analysis revealed that baseline 25(OH)D could predict HbA1c levels, weight regain and T2DM remission one-year post-surgery, accounting for 7.5% of HbA1c divergence (p < 0.01). These data highlight that higher circulating 25(OH)D levels are associated with significant metabolic health improvements post-surgery, notably, that such baseline levels are able to predict those who attain T2DM remission. This highlights the importance of 25(OH)D as a predictive biomarker of post-surgery benefits.
MeSH term(s)	Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/surgery ; Female ; Gastrectomy/methods ; Gastric Bypass/methods ; Glycated Hemoglobin/analysis ; Humans ; Male ; Obesity, Morbid/surgery ; Retrospective Studies ; Vitamin D ; Vitamins ; Weight Gain
Chemical Substances	Glycated Hemoglobin A ; Vitamins ; Vitamin D (1406-16-2)
Language	English
Publishing date	2022-05-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14102052
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Article ; Online: Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes.

Al-Daghri, Nasser M / Abdi, Saba / Sabico, Shaun / Alnaami, Abdullah M / Wani, Kaiser A / Ansari, Mohammed G A / Khattak, Malak Nawaz Khan / Khan, Nasiruddin / Tripathi, Gyanendra / Chrousos, George P / McTernan, Philip G

Biomolecules

2021 Volume 11, Issue 11

Abstract: Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence ... ...

Abstract	Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM:
MeSH term(s)	Aging ; Diabetes Mellitus, Type 2 ; Endotoxins ; Humans ; Middle Aged ; Telomere
Chemical Substances	Endotoxins
Language	English
Publishing date	2021-11-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11111693
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Article ; Online: Endotoxemia, vitamin D and premature biological ageing in Arab adults with different metabolic states

Nasser M. Al-Daghri / Shaun Sabico / Mohammed G.A. Ansari / Saba Abdi / Gyanendra Tripathi / George P. Chrousos / Philip G. McTernan

Saudi Journal of Biological Sciences, Vol 29, Iss 6, Pp 103276- (2022)

2022

Abstract	There are limited studies on the association of endotoxin, a potent mediator of gut-derived inflammation and telomere length (TL). We investigated (1) the influence of adiposity on endotoxin and TL amongst Saudi adults according to type 2 diabetes mellitus (T2DM) status and (2) the influence vitamin D may have on TL attrition. Anthropometric data and fasting blood samples were taken from 775 Saudi adults visiting different primary care centers in Riyadh [387 T2DM and 388 non-T2DM]. TL, derived from peripheral blood mononuclear cells, was analyzed by Quantitative real-time polymerase chain reaction and circulating endotoxin levels by Limulus Amebocyte Lysate assay. Subjects were stratified based on obesity and T2DM status. A significant lower TL was observed in the non-obese T2DM group as compared with their non-obese, non-T2DM counterparts (p = 0.002). Significant inverse associations between TL, endotoxin and endotoxin activity were observed in the cohort with obesity. Regression analysis showed that endotoxin was a significant predictor for TL in all subjects and even after stratification according to subgroups; with variances perceived in circulating TL stronger among non-T2DM obese (10%; p = 0.003) than non-T2DM non-obese (12%; p = 0.007). Also, in the non-T2DM group, TL and HDL-cholesterol predicted 29% of the variances perceived in 25(OH)D (p < 0.001). Taken together these findings show that circulating endotoxin and 25(OH)D are associated with premature biological ageing influenced by adiposity and metabolic state; suggesting future intervention studies to manipulate gut microbiome and or vitamin D levels may offer ways to mitigate premature TL attrition.
Keywords	Telomere length ; Endotoxin ; Endotoxin/HDL-Cholesterol ratio ; Systemic inflammation ; Oxidative stress ; Age ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Response to comment on: Harte et al. High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes Care 2012;35:375-382.

Harte, Alison L / McTernan, Philip G

Diabetes care

2013 Volume 36, Issue 3, Page(s) e43

MeSH term(s)	Diabetes Mellitus, Type 2/blood ; Diet, High-Fat/adverse effects ; Endotoxins/blood ; Female ; Humans ; Male
Chemical Substances	Endotoxins
Language	English
Publishing date	2013-02-20
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc12-2301
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Article ; Online: Sleep Quality Is Associated with Vitamin B12 Status in Female Arab Students.

Al-Musharaf, Sara / Alabdulaaly, Alanoud / Bin Mujalli, Hanadi / Alshehri, Hatoun / Alajaji, Hind / Bogis, Rania / Alnafisah, Ruyuf / Alfehaid, Shaden / Alhodaib, Hala / Murphy, Alice M / Hussain, Syed Danish / Sabico, Shaun / McTernan, Philip G / Al-Daghri, Nasser

International journal of environmental research and public health

2021 Volume 18, Issue 9

Abstract: Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep ... ...

Abstract	Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep among female college students in Saudi Arabia. In this cross-sectional study, we enrolled 355 participants (age (years), 20.7 ± 1.5; body mass index, 23.6 kg/m
MeSH term(s)	Aged ; Arabs ; Child ; Cross-Sectional Studies ; Female ; Humans ; Saudi Arabia/epidemiology ; Sleep ; Students ; Vitamin B 12 ; Young Adult
Chemical Substances	Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2021-04-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1660-4601
ISSN (online)	1660-4601
DOI	10.3390/ijerph18094548
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