Fat distribution and storage: how much, where, and how?
The Diabetes Center and the Department of Pediatrics, Hadassah Hebrew University School of Medicine, PO Box 12000, Jerusalem 91120, Israel (Correspondence should be addressed to R Weiss; Email: firstname.lastname@example.org)
Obesity does not necessarily imply disease and similarly obese individuals may manifest obesity-related morbidity or seemingly be in reasonably good health. Recent studies have shown that patterns of lipid partitioning are a major determinant of the metabolic proﬁle and not just obesity per se. The underlying mechanisms and clinical relevance of lipid deposition in the visceral compartment and in insulinsensitive tissues are described. Increased intramyocellular lipid deposition impairs the insulin signal transduction pathway and is associated with insulin resistance. Increased hepatic lipid deposition is similarly associated with the majority of the components of the insulin resistance syndrome. The roles of increased circulating fatty acids in conditions of insulin resistance and the typical pro-inﬂammatory milieu of speciﬁc obesity patterns are provided. Insights into the patterns of lipid storage within the cell are provided along with their relation to changes in insulin sensitivity and weight loss. European Journal of Endocrinology 157 S39–S45
The prevalence of obesity among adults as well as children is on the rise and gaining epidemic proportions (1). There is an overall consensus based on numerous longitudinal studies that obesity poses a signiﬁcant risk factor for the development of cardiovascular disease, alterations in glucose metabolism, certain cancers, intellectual deterioration, and reduces life expectancy. Despite these observations, a signiﬁcant proportion of obese individuals can achieve longevity without developing any of the morbidities previously mentioned. One hypothesis to explain this observation is that total body fat is not the sole source of the adverse health complications of obesity; rather the fat distribution or the relative proportion of lipids in various potential lipid deposition compartments is what determines the metabolic risk of the individual. Lipid deposition is an evolutionary advantageous process that allows efﬁcient storage of maximal calories per unit volume of tissue. The classic compartment intended for storage of excess calories is subcutaneous fat tissue that potentially also serves as insulation in the face of cold temperatures. The capacity to store lipid within the s.c. tissue is the key to facing famine and limited caloric supply on the one hand and to handling excess calories on the other. In cases where s.c. fat reaches a threshold beyond which it can store no more, lipids may be shunted to other depots. In that scenario, lipids may be stored in less advantageous This paper was presented at the Ipsen symposium, ‘The evolving biology of growth and metabolism’, Lisbon, Portugal, 16–18 March 2007. Ipsen has supported the publication of these proceedings.
compartments such as the intra-abdominal (visceral) compartment, and in insulin-sensitive tissues that are prone to deposition of lipid in speciﬁc clinical scenarios. This may cause deposition of lipid within skeletal muscle and the liver, affecting their normal metabolic pathways. This review focuses on the metabolic impact of overall adiposity and speciﬁcally lipid partitioning in the s.c. tissue, visceral compartment, muscle and liver on metabolic complications of obesity. The importance and clinical relevance of each compartment are highlighted with regards to the metabolic manifestations associated with each partitioning proﬁle. Insights into the dynamics of the morphology of lipid storage within muscle are described. The ‘sub-clinical’ inﬂammation characteristic of increased body fat is discussed. The majority of examples are from studies...