This study will evaluate the importance of insulin resistance in the development of CVD and diabetes, and has implications for the development of prevention and treatment strategies.

Oedema is a common finding in obesity and its cause is not always clear. Possible causes include impairment of cardiac, respiratory and/or renal function, chronic venous insufficiency and lymphatic problems. Lymphoscintigraphy is the best method to detect structural lymphatic abnormalities that can cause lymphoedema. We reviewed 49 female subjects with pitting oedema who had undergone lymphoscintigraphy, divided in three groups. The first group was comprised of severely obese patients in whom cardiorespiratory causes for oedema had been excluded. The second group consisted of non-obese patients with recognized causes for oedema and the third group was non-obese patients with 'idiopathic' oedema. A standard classification was used to interpret lymphoscintigraphy results. The frequency and severity of lymphoscintigraphic abnormalities was greatest in patients with clinical diagnoses of oedema related to 'recognized causes' (any abnormality in 50% of legs with obstruction in 22%). Obese patients and those with 'idiopathic'oedema had fewer (P ¼ 0.02 for both) and milder lymphoscintographic abnormalities (any abnormality 32 and 25%, respectively, obstruction 5 and 3%, respectively), and although the clinical oedema was invariably bilateral, the lymphoscintigraphy abnormalities were usually unilateral. In conclusion, structural lymphoscintigraphic abnormalities are uncommon in obesity and do not closely correlate with the clinical pattern of oedema.

Pfeiffer and colleagues years ago pointed out that different distributions and amounts of adipose tissue are associated with abnormalities of lipolysis and lipoprotein metabolism. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6. These adipose tissue actions are crucially regulated by nutrition. The review considers the existence of metabolic pathways and modes of regulation within adipose tissue, and how such metabolic activity can be quantitated in humans. Nutrition can influence adipose tissue at several 'levels'. Firstly the level of obesity or malnutrition has important effects on many aspects of adipose tissue metabolism. Secondly short-term overfeeding, underfeeding and exercise have major impacts on adipose tissue behaviour. Lastly, specific nutrients are capable of regulating adipose tissue metabolism. Recently there have been considerable advances in understanding adipose tissue metabolism and in particular its regulation. This review discusses the behaviour of adipose tissue under various nutritional conditions. There is then a review of recent work examining the ways in which nutritional influences act via intra-cellular mechanisms, insulin and the sympathetic innervation of adipose tissue.

The landmark discovery of leptin established beyond question the fact that adipose tissue is a crucial active regulator of body weight, an endocrine organ in its own right and part of a feedback circuit possessing both afferent and efferent loops. This is in addition to its more established roles as a receiver of incoming endocrine signals and modulator of circulating hormones such as sex steroids. Since this discovery, much has been learned about the role of leptin in the afferent loop of the hypothalamic regulation of body weight and indeed about some of the neuro-endocrine circuitry involved in the regulation of appetite and weight. Much less, however, is known about the efferent limb of the circuit, specifically relating to how the hypothalamus is able to influence adipocyte behaviour and how this link may itself be influenced by endocrine and paracrine signals, both acting on and emanating from adipocytes themselves, acting at multiple levels. This review will focus on the role of the sympathetic nervous system (SNS) and adreno-medullary system in relation to the regulation of adipose tissue physiology and endocrine function. The evidence in support of the hypothesis that the SNS is a crucial mediator of the efferent loop of this feedback circuit will be considered.