ORCID Profile
0000-0002-5477-8585
Current Organisations
University College London
,
Imperial College London
,
University College Hospital
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Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 08-2002
DOI: 10.1038/NATURE00887
Publisher: Elsevier BV
Date: 10-2019
Publisher: Springer Science and Business Media LLC
Date: 15-05-2023
DOI: 10.1038/S41467-023-38439-Z
Abstract: DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 s les, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 1 × 10-7). We connect obesity-associated methylation variations to transcriptomic changes at target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.CMET.2006.08.001
Abstract: Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity.
Publisher: American Diabetes Association
Date: 13-05-2016
DOI: 10.2337/DC16-0236
Abstract: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005–30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28–30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m2) and in those with class II obesity (BMI 35.0–39.9 kg/m2) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0–34.9 kg/m2 if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m2 for Asian patients. Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.
Publisher: Humana Press
Date: 2005
Publisher: Wiley
Date: 10-10-2007
Abstract: Recent evidence suggests that alterations in insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) can increase mammalian life span. For ex le, in several mouse mutants, impairment of the growth hormone (GH)/IGF1 axis increases life span and also insulin sensitivity. However, the intracellular signaling route to altered mammalian aging remains unclear. We therefore measured the life span of mice lacking either insulin receptor substrate (IRS) 1 or 2, the major intracellular effectors of the IIS receptors. Our provisional results indicate that female Irs1-/- mice are long-lived. Furthermore, they displayed resistance to a range of age-sensitive markers of aging including skin, bone, immune, and motor dysfunction. These improvements in health were seen despite mild, lifelong insulin resistance. Thus, enhanced insulin sensitivity is not a prerequisite for IIS mutant longevity. Irs1-/- female mice also displayed normal anterior pituitary function, distinguishing them from long-lived somatotrophic axis mutants. In contrast, Irs2-/- mice were short-lived, whereas Irs1+/- and Irs2+/- mice of both sexes showed normal life spans. Our results therefore suggest that IRS1 signaling is an evolutionarily conserved pathway regulating mammalian life span and may be a point of intervention for therapies with the potential to delay age-related processes.
Publisher: BMJ
Date: 06-07-2018
DOI: 10.1136/THORAXJNL-2017-211073
Abstract: To characterise the sketetal muscle metabolic phenotype during early critical illness. Vastus lateralis muscle biopsies and serum s les (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5). From day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (−27.4CN (95% CI −123.9 to 14.3) n=23 p=0.025) and mitochondrial DNA copy number (−1859CN (IQR −5557–1325) n=35 p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9) p .001) and decreased over 7 days (−4.8 mmol/kg dw (IQR −8.0–1.2) n=33 p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR −0.09–2.6) n=31 p .001). There was an increase in intramuscular phosphocholine (847.2AU (IQR 232.5–1672) n=15 p=0.022), intramuscular tumour necrosis factor receptor 1 (0.66 µg (IQR −0.44–3.33) n=29 p=0.041) and IL-10 (13.6 ng (IQR 3.4–39.0) n=29 p=0.004). Serum adiponectin (10.3 µg (95% CI 6.8 to 13.7) p .001) and ghrelin (16.0 ng/mL (IQR −7–100) p=0.028) increased. Network analysis revealed a close and direct relationship between bioenergetic impairment and reduction in muscle mass and between intramuscular inflammation and impaired anabolic signaling. ATP content and muscle mass were unrelated to lipids delivered. Decreased mitochondrial biogenesis and dysregulated lipid oxidation contribute to compromised skeletal muscle bioenergetic status. In addition, intramuscular inflammation was associated with impaired anabolic recovery with lipid delivery observed as bioenergetically inert. Future clinical work will focus on these key areas to ameliorate acute skeletal muscle wasting. NCT01106300 .
Publisher: Springer Science and Business Media LLC
Date: 27-10-2021
DOI: 10.1038/S41575-021-00523-4
Abstract: Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Rachel Batterham.