Central regulation of energy balance: inputs, outputs and leptin resistance

Abstract

The regulation of energy balance is complex and, in man, imprecise. Nevertheless, in many individuals intake and expenditure are balanced with <1% error with little or no conscious effect. Essential components of such a regulatory system are signals, leptin and insulin, that reflect the size of lipid stores. Leptin receptors signal via phosphatidylinositol 3-kinase (as do insulin receptors) and via the transcription factor signal transducer and activator of transcription-3 to activate various types of neurone. Obese rodents, and possibly man, are resistant to leptin; in some cases because of genetic or perinatal programming (primary resistance), but commonly in response to high leptin levels (secondary resistance). Secondary leptin resistance may be a result of reduced transport of leptin to the brain or down-regulation of leptin signalling. Signals that reflect lipid stores form the tonic homeostatic regulatory system. They interact with episodic homeostatic signals carried by neurones, hormones and metabolites to regulate meal size and frequency. They also interact with signals related to the palatability of food, biorhythms and learning. Many neurotransmitters and hormones mediate responses to more than one input (e.g. gastric and adipocyte leptin), but are nevertheless most involved with particular inputs (e.g. leptin with adipocyte fat stores). Feeding can be divided into appetitive (preparation for feeding) and consummatory phases, which can both be further subdivided. Different sets of neurotransmitters and hormones are involved at each stage. In the long term it may be possible to customise obesity therapies according to those inputs and outputs that are most disturbed and most amenable to intervention in individual subjects.

Body mass index and serum leptin concentration independently estimate percentage body fat in older adults

“…The flattening of the leptin curves reflects a greater increase in leptin per unit increase in percentage fat at higher levels of percentage fat. This is consistent with leptin resistance that occurs in most obese persons (22,23). Substituting height and weight, or the FIGURE 3.…”

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

“…Recent work has linked leptin resistance to both reduced leptin transport across the blood brain barrier as well as reduced leptin signaling (Arch, 2005;Banks et al, 2004;Banks and Farrell, 2003;Feng, 2006;Steinberg et al, 2006). However, the presence of leptin resistance in our study population would most likely serve to negatively confound our analysis, masking an even more robust association between higher leptin levels and reduced likelihood of cognitive decline.…”

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice

“…Mature adipocytes produce adiponectin, which increases insulin sensitivity, glucose uptake, fatty acid oxidation, and anti-inflammatory effects in hormone-stimulated lipolysis [25] . To prevent lipid accumulation in adipose tissue, adipocytes secrete leptin to regulate food intake and fatty acid oxidation contacted with brain [26] . The plasma concentration of adipose tissues and endocrine hormones revealed that GCBE treatment reduced leptin concentrations and inversely increased adiponectin, in a dose dependent manner.…”