Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin.

Recent research suggests that increased adiposity is associated with poor cognitive performance, independently of associated medical conditions. The evidence regarding this relationship is examined in this review article. A relatively consistent finding across the lifespan is that obesity is associated with cognitive deficits, especially in executive function, in children, adolescents and adults. However, as illustrated by contradictory studies, the relationship between obesity and cognition is uncertain in the elderly, partly because of inaccuracy of body mass index as a measure of adiposity as body composition changes with aging. This review further discusses whether obesity is a cause or a consequence of these cognitive deficits, acknowledging the possible bidirectional relationship. The possible effects of increased adiposity on the brain are summarized. Our investigations suggest that weight gain results, at least in part, from a neurological predisposition characterized by reduced executive function, and in turn obesity itself has a compounding negative impact on the brain via mechanisms currently attributed to low-grade systemic inflammation, elevated lipids and/or insulin resistance. The possible role of cognitive remediation treatment strategies to prevent and/or treat obesity is discussed.

Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of "M1" or "classically activated" macrophages. Furthermore, macrophages have been identified as the primary source of many of the circulating inflammatory molecules that are detected in the obese state and are postulated to be causal both in the development of insulin resistance and in the progression to type 2 diabetes. There is also novel evidence to suggest that macrophages inhibit adipocyte differentiation, potentially leading to adipocyte hypertrophy, altered secretion of adipokines and ectopic storage of lipid within liver, muscle and other non-adipose tissues. Currently, it is not clear what causes increased macrophage infiltration of adipose tissue in obese individuals. Theories include altered signalling by adipocytes, nutritional induction of metabolic endotoxemia or reduced angiogenesis and local adipose cell hypoxia. Importantly, PPAR-gamma agonists have been shown to alter macrophage phenotype to "M2" or an "alternatively activated" anti-inflammatory phenotype and may induce macrophage specific cell death. Consequently, excitement surrounds the potential for specific inhibition of macrophage infiltration of adipose tissue via pharmacotherapy for obese patients and more particularly as adjunct therapy to improve insulin sensitivity in obese individuals with insulin resistance and overt type 2 diabetes.