Title: Predicting Metabolic Risk and Correlations with Cognitive Function in Mexican Pre-pubertal Children (METCOG)
Funder: Medical Research Council

Abstract: BACKGROUND Over 30% of children in Mexico and the UK are overweight/obese, with a third likely to be obese as adults. Obese individuals are more likely to develop disorders such as, high blood pressure, diabetes, increased harmful fat in the blood (dyslipidaemia), fatty liver, inflammation, heart disease and some forms of cancer. Furthermore, abdominal obesity (fat around the waist), high fat/sugar feeding as well as liver disease have been reported to lead to dysfunction in cognitive capabilities (difficulties in learning, thinking and memory). Whether the inflammation observed in obesity links the body and brain effects remains to be determined. Body fat can be stored in specific areas, including under the skin, around certain organs as well as inside organs such as the liver. Obesity is defined the excessive build-up of body fat in these tissues. While obese individuals are more likely to be unhealthy, rather surprisingly, 1 in 5 seems to show resistance to developing clinical complications. This appears to arise from the fact that some of them may have lower amounts of fat around their abdomen. Thus, it is not only the amount but also the distribution of body fat that may better predict the risk of developing obesity-related diseases. Conventionally, a person is defined as overweight/obese by their body-mass index (BMI), skin thickness or waist-to-hip ratio. These methods are however very poor predictors of the amount and distribution of body fat. Magnetic resonance imaging (MRI) can be used to safely look into the body and can very accurately measure the amount and distribution of fat in the body as well as the amount of fat inside a person's liver. Fatty liver is often inflamed and may have fibrous deposits (fibrosis) which can exacerbate the clinical condition of an overweight/obese person. At present, little is known as to the levels and distribution of body fat in overweight/obese children as MRI techniques have not been implemented in such a group of subjects. Similarly, there is no information as to the extent to which these children have accumulated fat in their liver. Nor is there much information as to how this abnormal deposition of body fat affects their cognitive abilities. AIMS AND OBJECTIVES We aim to identify accurate predictors of the risk of developing physical and cognitive problems in children with a range of body weights as well as whether changes in inflammation seen in obesity links abnormal body fat deposition and changes in brain function. We will focus on pre-pubertal children to negate the varied effects of hormones during puberty on different measurements. Objectives are to: (1) use MRI to measure the pattern of body fat deposition in normal weight, overweight and obese children; (2) correlate fat measures with blood levels of glucose, bad fats, molecules produced by fat cells as well as those molecules involved in inflammation; (3) correlate different fat depots with blood inflammatory markers and liver inflammation with cognitive abilities; (4) use experimental models of obesity (i) to determine the strength of the association between fat deposition, blood measures, blood and liver inflammation measures with brain inflammation and behaviour tests and (ii) assess whether early-life rather than later-life obesity significantly increases the risk of developing physical and cognitive dysfunction in adulthood. POTENTIAL APPLICATIONS AND BENEFITS The early identification of children at greater risk of future health problems enables earlier intervention which is likely to be more successful by avoiding cumulative harmful processes that may be more resistant to intervention. The obesity epidemic, alongside childhood obesity, and the ageing population, means that the outputs from this project will greatly benefit the welfare and socio-economics of Mexico and the UK, as well


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE