Introduction While obesity has become a major public health concern, particularly in adolescents, the prevalence of hypertension has been increasing ( Egan et al . 2010 , Shay et al . 2013 , Zhao et al . 2013 ). Accumulating evidence has shown
Zhi Zhang, Fang Wang, Bing-jian Wang, Guang Chu, Qunan Cao, Bao-Gui Sun and Qiu-Yan Dai
M Igel, BA Taylor, SJ Phillips, W Becker, L Herberg and HG Joost
KK obese mice exhibit a multigenic syndrome of moderate obesity, hyperinsulinemia and hyperglycemia. Here we show that the syndrome is accompanied by a marked elevation of leptin protein in adipose tissue, as well as leptin levels in serum, which corresponds with the degree of obesity. The cDNA sequence of leptin is normal in KK mice, whereas three nucleotide polymorphisms were found in the cDNA of the leptin receptor, one of them resulting in exchange of an aspartate residue for asparagine (Asp600Asn) in a highly conserved part of the second extracellular cytokine-receptor homology module. In female (but not male) F2 mice of a C57BL/6JxKK intercross, the weight of gonadal, retroperitoneal and mesenteric adipose tissue was positively correlated with the number of alleles inherited from the KK parental strain at a microsatellite marker (D4Mit175) which maps close (0.7 centimorgan proximal) to the leptin receptor gene. It is suggested that the Asp600Asn leptin receptor variant contributes to the obesity syndrome in KK female mice, but that its contribution is only a part of the multigenic syndrome.
J. U. Weaver, G. A. Hitman and P. G. Kopelman
Obesity is likely to be a multifactorial disease with an important genetic component. Animal models of genetic and experimentally induced obesity suggest that glucocorticoid receptor (GR) activity plays a role in the aetiology and maintenance of the obese state. Glucocorticoid activity appears to be essential for the development of hyperinsulinaemia and subsequent fat deposition. In humans, glucocorticoid excess is associated with central fat distribution. We have therefore investigated the restriction fragment length polymorphisms of the human GR gene locus (GRL) and have sought associations of specific alleles with anthropometric measurements and indices of insulin secretion and resistance in obesity.
Fifty-six extremely obese, unrelated, nondiabetic premenopausal British Caucasian females and 43 age-matched, normal weight controls were studied. The obese subjects were characterized by fat distribution (waist to hip ratio), insulin secretion and insulin resistance (fasting insulin (FI)), an index of insulin resistance (HOMA), stimulated insulin secretion during an oral glucose tolerance test and insulin-mediated glucose disposal, steady-state plasma glucose). A BclI polymorphism (fragments of 4·5 and 2·3 kb) demonstrated significant association with indices of glucose metabolism in obesity; those subjects homozygous for the 4·5 kb fragment had elevated FI (Pc=0·012) and HOMA (Pc=0·012) values. The genotypic and allelic frequencies of the GRL BclI polymorphism were otherwise similar in obese and normal weight subjects. We postulate that the GRL BclI polymorphism may directly affect GR gene expression, or be in linkage disequilibrium with a possible mutation within one of three exons of the GR gene, and thereby modulate GR transcriptional activity on target genes involved in glucose and insulin homeostasis.
Dhivya Kumar, Richard E Mains and Betty A Eipper
, or degraded in lysosomes. PAM, cilia, and POMC in obesity A close look at the phylogenetic distribution of PAM suggested a strong correlation with the presence of cilia, leading us to explore the presence of PAM in this signaling
). There are mainly two types of adipose tissues. (1) The fat-storing white adipose tissue (WAT), which expands under obese conditions and becomes inflammatory, leading to insulin resistance and (2) the fat-burning brown adipose tissue (BAT), which is rich
T. Sawa, S. Ohgaku, H. Morioka and S. Yano
Two insulin genes of the NON mouse, an animal model of human non-obese, non-insulin-dependent diabetes mellitus, were isolated and characterized to examine the hypothesis that these genes are structurally different from those of normal mice. The NON mouse was found to have two non-allelic insulin genes, as does the normal mouse, and no structural differences were found between the normal and NON mouse in the nucleotide sequence of the insulin gene, including that of the 5′-transcriptional regulatory region, and in the deduced amino acid sequence. There was, however, an additional 113 bp sequence and seven point mutations in a further 5′-flanking region, and three point mutations in the 3′-flanking region of the insulin II gene. We conclude that reduced expression of insulin genes in the NON mouse is not due to the structural change in the known transcriptional regulatory region, although the effect on insulin II gene expression of an additional sequence upstream of the 5′-flanking region, as the negative regulatory factor, remains to be elucidated.
, and, therefore, the suggestion has been put that it has potential as an anti-obesity strategy in humans. The problem is that previous attempts to target human BAT through the sympathetic nervous system (SNS) have proven unsafe. This review aims to draw
James Paterson, Ian R Kelsall and Patricia T W Cohen
age, whereas the mice of Delibegovic et al . (2003) were obese with large abdominal fat deposits, glucose intolerant and insulin resistant at 11–12 months of age, and glucose uptake into skeletal muscle in vivo was decreased. This prediabetic
Fei Xiao, Ying Du, Ziquan Lv, Shanghai Chen, Jianmin Zhu, Hongguang Sheng and Feifan Guo
Introduction Obesity has become a leading public health problem in many countries around the world. One of the important factors that contributes to obesity is dietary macronutrient including fat, glucose and amino acids (AAs) ( Attie
N T Lam, S D Covey, J T Lewis, S Oosman, T Webber, E C Hsu, A T Cheung and T J Kieffer
the dual role of PTP1B in attenuating leptin and insulin signaling, there is great interest in pursuing PTP1B inhibition to treat both obesity and diabetes ( Johnson et al. 2002 , Zhang & Lee 2003 ). However, the relative importance of PTP1B