Turning over our fat stores: the key to metabolic health Blaxter Award Lecture 2018.

The present paper results from my receiving the Nutrition Society's first Blaxter Award, and describes briefly my academic history. My interest in human fat metabolism began in the Medical Research Council's Trauma Unit, studying metabolic changes in critically ill patients and their responses to nutrition. On moving to Oxford in 1986, I began to study pathways for depositing fat in adipose tissue. This involved the development of new methodologies, in particular, a technique for measurement of arterio-venous differences of metabolite concentrations across human adipose tissue beds, primarily the subcutaneous anterior abdominal depot. Our early studies showed that this tissue is dynamic in its metabolic behaviour, responding rapidly (within minutes) to changes in nutritional state. This led to an understanding of adipose tissue as playing an essential role in metabolic health, by capturing incoming dietary fatty acids, storing them as TAG and releasing them when needed, analogous to the role of the liver in glucose metabolism; we called this 'buffering' of fatty acid fluxes. In obesity, the mass of adipose tissue expands considerably, more than is often appreciated from BMI values. We confirmed other observations of a strong suppression of release of NEFA from adipose tissue in obesity, tending to normalise circulating NEFA concentrations. A corollary, however, is that fatty acid uptake must be equally suppressed, and this disrupts the 'buffering' capacity of adipose tissue, leading to fat deposition in other tissues; ectopic fat deposition. This, in turn, is associated with many metabolic abnormalities linked to obesity.