Disease relevance of Adip1

• Adip8 interacts with all the other adiposity QTLs and seems to play a central role in the genetic system affecting obesity in this cross [1].
• Oral administration of a mimetic in a mouse model of high-fat diet-induced obesity reduced body weight gain, adiposity and insulin resistance [2].
• Nmu(-/-) mice showed increased body weight and adiposity, hyperphagia, and decreased locomotor activity and energy expenditure [3].
• This reduced weight gain was associated with decreased adiposity and increased energy expenditure and locomotor activity as the animals aged [4].
• Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality [5].

Psychiatry related information on Adip1

• For example, ghrelin levels rise following food deprivation, and ghrelin administration stimulates feeding and increases body weight and adiposity [6].
• The lack of hypocretin signaling is the cause of narcolepsy while elevated hypocretin levels induce arousal, elevated food intake, and adiposity [7].

High impact information on Adip1

• We show here that targeted activation of PPARdelta in adipose tissue specifically induces expression of genes required for fatty acid oxidation and energy dissipation, which in turn leads to improved lipid profiles and reduced adiposity [8].
• These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling [9].
• The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity [9].
• Neuronal Ptpn1(-/-) mice have reduced weight and adiposity, and increased activity and energy expenditure [10].
• Furthermore, an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity [11].

Chemical compound and disease context of Adip1

• These changes correlated with reduced body adiposity, hepatomegaly and steatosis, and postprandial plasma insulin and glucose levels [12].
• Despite a normal level of leptin receptors in the hypothalamus and normal food intake, mutant mice developed increased adiposity, decreased body temperature, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and insulin sensitivity, as well as elevated hepatic and skeletal muscle triglyceride levels [13].
• The human FAS gene (FAS) maps to chromosome 17q25, a region previously shown to have suggestive linkage to adiposity in a genome-wide linkage scan for genetic determinants of obesity in Pima Indians [14].
• Moreover, the increased calcitriol produced in response to low-calcium diets stimulates adipocyte Ca(2+) influx and, consequently, promotes adiposity, whereas higher-calcium diets inhibit lipogenesis, inhibit diet-induced obesity in mice, and promote lipolysis, lipid oxidation, and thermogenesis [15].
• In humans, circulating lipocalin-2 concentrations were positively correlated (P <0.005) with adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index, but negatively correlated (P = 0.002) with HDL cholesterol [16].

Biological context of Adip1

• We map body composition traits, adiposity, and skeletal size, in a replicate F2 intercross of the same two strains containing 510 individuals [1].
• We have inactivated the Y5R gene in mice and report that younger Y5R-null mice feed and grow normally; however, they develop mild late-onset obesity characterized by increased body weight, food intake and adiposity [17].
• Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear [18].
• As leptin levels rise with increasing adiposity in rodents and man, it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance [19].
• Transgenic mice expressing lower levels of the transgene had normal adiposity and survived to adulthood; however, they showed a complete resistance to chemically induced obesity [20].

Anatomical context of Adip1

• Adrenaline and noradrenaline, the main effectors of the sympathetic nervous system and adrenal medulla, respectively, are thought to control adiposity and energy balance through several mechanisms [21].
• To investigate the interrelationship between excessive adipose tissue mass and these associated disorders, we have attempted to reduce adiposity via targeted expression of an attenuated diphtheria toxin A chain to adipose tissue, using the 5' regulatory region of the adipocyte P2 (aP2) gene [20].
• The adipocyte-derived hormone leptin and the pancreatic beta cell-derived hormone insulin each function as afferent signals to the hypothalamus in an endocrine feedback loop that regulates body adiposity [22].
• While adult male mice lacking phosphatidylinositol 5-phosphate 4-kinase beta have significantly less body fat than wild-type littermates, female mice lacking phosphatidylinositol 5-phosphate 4-kinase beta have increased insulin sensitivity in the presence of normal adiposity [23].
• We conclude that, although mGPD is not essential for thyroid thermogenesis, variations in its function affect viability and adiposity in mice [24].

Associations of Adip1 with chemical compounds

• Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise [25].
• Since fat oxidation in non-adipose tissue can influence body adiposity, we sought to determine whether d4T, AZT and BAIBA can cause lipoatrophy in mice by this catabolic mechanism [26].
• The aim of this study was to determine whether the human PPAR gamma proline to alanine substitution polymorphism (Pro12Ala) modifies the association between dietary fat and adiposity and plasma lipids [27].
• Mice that lack acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride synthesis, have decreased adiposity and increased insulin sensitivity [28].
• To address this issue, effects of central, chronic treatment with histamine on food intake, adiposity, and energy expenditure were examined using leptin-resistant obese and diabetic mice [29].

Regulatory relationships of Adip1

• The Y5R antagonist selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body weight gain and adiposity while improving the DIO-associated hyperinsulinemia [30].
• This study demonstrates that Agtr1a-/- mice exhibit attenuation of diet-induced weight gain and adiposity through increased energy expenditure [31].
• Thus, PTP1B regulates body mass and adiposity primarily through actions in the brain [10].
• However, a synergistic interaction between Y2 and Y4 pathways seems to regulate bone volume and adiposity and could have important implications for possible interventions in obesity and for anabolic treatment of osteoporotic bone loss [32].
• Adipocyte-selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance [13].

Other interactions of Adip1

• Two of these adiposity loci also affected tail length (Adip4 and Adip6) along with seven additional tail length QTLs (Skl1-7) [1].
• Similar effects on body weight and adiposity were also observed in female, but not male, GHSR-null mice fed standard chow [6].
• Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice [33].
• In obese mice matched for adiposity, Ccr2 deficiency reduced macrophage content and the inflammatory profile of adipose tissue, increased adiponectin expression, ameliorated hepatic steatosis, and improved systemic glucose homeostasis and insulin sensitivity [34].
• Gcgr(-/-) mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure [35].

Analytical, diagnostic and therapeutic context of Adip1

• These data demonstrate the feasibility of gentle manipulation of adiposity and allow a functional dissection of obesity and its metabolic sequelae [20].
• Here we show that the transplantation of DGAT1-deficient WAT decreases adiposity and enhances glucose disposal in wild-type mice [36].
• Leptin may contribute to the correlation between adiposity and malignancies as its levels are usually increased in obese subjects and reduced by caloric restriction [37].
• This concept of calcium modulation of adiposity was further evaluated epidemiologically in the NHANES III data set [38].
• Many people supplement their diets with CLAs to attempt weight loss, and the trans-10,cis-12 isomer (t10,c12-CLA) of CLA reduces adiposity in animal models and humans [39].

References