No conclusive evidence for association of polymorphisms in the adiponectin receptor 1 gene, AdipoR1, with common obesity.

AdipoR1 is one of the adiponectin receptors which are important for adiponectin signaling. Because adiponectin is a candidate gene for common obesity, it is also hypothesized that variations in AdipoR1 may be involved in the development of complex obesity. Therefore, we designed an association study for the AdipoR1 gene. We performed a case-control association study including 1,021 obese subjects (mean age 42 ± 12 years; mean BMI 38.2 ± 6.2 kg/m²) and 226 lean, healthy individuals (mean age 36 ± 7 years; mean BMI 22.1 ± 1.7 kg/m²). Nine tagSNPs were selected to cover the entire AdipoR1 gene and surrounding 7 kb region (based on HapMap data). TagSNPs were genotyped using AcycloPrime-Fluorescence Polarization (FP) SNP Detection kits and TaqMan Pre-Designed SNP Genotyping assays according to manufacturer's protocols. We found that the rs1075399 non-reference allele decreases obesity risk by 45 % in men only [odds ratio (OR) = 0.55, 95 % CI 0.35-0.87, nominal P = 0.010]. However, after Bonferroni correction for multiple testing, this association is lost. None of the other tagSNPs were associated with obesity when studying the entire population, nor when looking at men and women separately. Quantitative analysis of the effect of each SNP on height, weight, and BMI revealed that none of the tagSNPs are associated with weight or BMI. We report here that we found no decisive evidence for association between AdipoR1 tagSNPs and complex obesity in our Belgian Caucasian population.

Promising new approaches to the management of obesity.

The pathophysiology of obesity is complex with many different pathways involved. A better understanding of these weight-regulating mechanisms has lead to the identification of new targets for anti-obesity agents. Most attention has been given to the centrally acting neuropeptides regulating food intake. Leptin, playing a key-role, exerts its action through several neuropeptides such as neuropeptide Y, alpha-melanocyte stimulating hormone and agouti related protein. Cocaine- and amphetamine-regulated transcript peptide and the orexins are the latest discovered peptides acting at the level of the hypothalamus. Targets for new drugs acting on peptides secreted from the periphery are cholecystokinin and glucagon-like peptide 1. Another potential target in the treatment of obesity is increasing energy expenditure via beta3 adrenoceptors or uncoupling proteins. These new pharmacological agents in development could be valuable adjuncts to more traditional treatment strategies such as dietary treatment, behavioural/psychological counselling and physical activity.

Overweight, obesity, and blood pressure: the effects of modest weight reduction.

Several large epidemiological studies have shown an association between body mass index and blood pressure in normal weight and overweight patients. Weight gain in adult life especially seems to be an important risk factor for the development of hypertension. Weight loss has been recommended for the obese hypertensive patient and has been shown to be the most effective nonpharmacological treatment approach. However, long-term results of weight loss programs are disappointing with people often regaining most of the weight initially lost. In recent years, a modest weight loss, defined as a weight loss of 5% to 10% of baseline weight, has received increasing attention as a new treatment strategy for overweight and obese patients. A more gradual and moderate weight loss is more likely to be maintained over a longer period of time. Several studies have confirmed the blood pressure-lowering effect of a modest weight loss in both hypertensive and nonhypertensive patients. A modest weight loss can normalize blood pressure levels even without reaching ideal weight. In patients taking antihypertensive medication, a modest weight loss has been shown to lower or even discontinue the need for antihypertensive medication. In patients with high normal blood pressure, a modest weight loss can prevent the onset of frank hypertension. The blood pressure-lowering effect of weight loss is most likely a result of an improvement in insulin sensitivity and a decrease in sympathetic nervous system activity and occurs independent of salt restriction. In conclusion, a modest weight loss that can be maintained over a longer period of time is a valuable treatment goal in hypertensive patients.

Clinical endocrinology of human leptin.

Since the discovery of leptin, a boom of scientific knowledge became available about the OB-protein gene and its role and significance in weight regulation. Both from animal and human research data, serum leptin can probably be considered as one of the best biological markers to reflect total body fat, and this finding is true over a wide range of body mass indexes (BMIs) and in different pathologies: in normal weight, anorexic and obese subjects; in non insulin-dependent diabetes mellitus (NIDDM) patients, PCO women, Prader-Willi children and subjects with hypogonadism and growth hormone deficiency. Gender differences clearly exist, probably related to sex hormone differences, and from fat distribution studies it could be shown that subcutaneous fat is much more related to serum leptin concentrations than visceral fat: also leptin messenger-RNA (m-RNA) expression is significantly higher in subcutaneous fat from human obese subjects. Leptin is not only correlated to a series of endocrine parameters such as insulin, insulin-like growth factor, (IGF) and SHBG, it seems involved as a mediator in some endocrine mechanisms (onset of puberty, insulin secretion, etc) as well. Weight loss will reduce human leptin concentrations, whereas the administration of human recombinant leptin seems to show only limited effects.