PMC:4195273 / 21266-24692 JSONTXT

{"project":"TEST0","denotations":[{"id":"25352770-233-241-357417","span":{"begin":672,"end":676},"obj":"[\"9590691\"]"},{"id":"25352770-233-241-357418","span":{"begin":694,"end":698},"obj":"[\"9661247\"]"},{"id":"25352770-235-243-357419","span":{"begin":714,"end":718},"obj":"[\"10612705\"]"},{"id":"25352770-225-233-357421","span":{"begin":741,"end":745},"obj":"[\"10650962\"]"},{"id":"25352770-235-243-357422","span":{"begin":761,"end":765},"obj":"[\"11684040\"]"},{"id":"25352770-231-239-357423","span":{"begin":778,"end":782},"obj":"[\"11959420\"]"},{"id":"25352770-230-238-357424","span":{"begin":800,"end":804},"obj":"[\"15659233\"]"},{"id":"25352770-229-237-357425","span":{"begin":823,"end":827},"obj":"[\"17124379\"]"},{"id":"25352770-234-242-357426","span":{"begin":845,"end":849},"obj":"[\"17669377\"]"},{"id":"25352770-190-198-357427","span":{"begin":1042,"end":1046},"obj":"[\"9590691\"]"},{"id":"25352770-210-218-357428","span":{"begin":1062,"end":1066},"obj":"[\"10537115\"]"},{"id":"25352770-235-243-357429","span":{"begin":1087,"end":1091},"obj":"[\"11024558\"]"},{"id":"25352770-227-235-357430","span":{"begin":1119,"end":1123},"obj":"[\"11850744\"]"},{"id":"25352770-234-242-357431","span":{"begin":1141,"end":1145},"obj":"[\"14700744\"]"},{"id":"25352770-120-128-357432","span":{"begin":1268,"end":1272},"obj":"[\"14700744\"]"},{"id":"25352770-229-237-357433","span":{"begin":1461,"end":1465},"obj":"[\"10482243\"]"},{"id":"25352770-233-241-357434","span":{"begin":1480,"end":1484},"obj":"[\"11043558\"]"},{"id":"25352770-233-241-357435","span":{"begin":1501,"end":1505},"obj":"[\"14730586\"]"},{"id":"25352770-173-181-357436","span":{"begin":1681,"end":1685},"obj":"[\"9883730\"]"},{"id":"25352770-179-187-357437","span":{"begin":1687,"end":1691},"obj":"[\"11241374\"]"},{"id":"25352770-227-235-357438","span":{"begin":2015,"end":2019},"obj":"[\"9796811\"]"},{"id":"25352770-231-239-357439","span":{"begin":2040,"end":2044},"obj":"[\"9590691\"]"},{"id":"25352770-234-242-357440","span":{"begin":2060,"end":2064},"obj":"[\"10537115\"]"},{"id":"25352770-235-243-357441","span":{"begin":2085,"end":2089},"obj":"[\"11024558\"]"},{"id":"25352770-232-240-357442","span":{"begin":2117,"end":2121},"obj":"[\"11850744\"]"},{"id":"25352770-235-243-357443","span":{"begin":2456,"end":2460},"obj":"[\"11113536\"]"},{"id":"25352770-235-243-357444","span":{"begin":2731,"end":2735},"obj":"[\"11113536\"]"},{"id":"25352770-229-237-357445","span":{"begin":3009,"end":3013},"obj":"[\"11850744\"]"},{"id":"25352770-230-238-357446","span":{"begin":3031,"end":3035},"obj":"[\"14700744\"]"},{"id":"25352770-228-236-357447","span":{"begin":3049,"end":3053},"obj":"[\"20626417\"]"},{"id":"25352770-228-236-357448","span":{"begin":3398,"end":3402},"obj":"[\"11850744\"]"},{"id":"25352770-234-242-357449","span":{"begin":3420,"end":3424},"obj":"[\"14700744\"]"}],"text":"While the role of CART in controlling appetite and energy homeostasis in the human system might be somewhat different, in rodents, the neuronal network in which CART is involved to modulate energy homeostasis has been well-described. The expression of endogenous CART at brain regions involved in feeding regulation has been shown to be sensitive to the energy balance status and the genetic background of mice. In brief, fasting has been documented in various mammals to reduce CART mRNA levels at the hypothalamic PVN, Arc, perifornical region, as well as the nucleus accumbens shell (AcbSh) of the striatum, whilst refeeding restored the expression (Kristensen et al., 1998; Lambert et al., 1998; Adams et al., 1999; Vrang et al., 1999a, 2000; Henry et al., 2001; Li et al., 2002; Yang and Shieh, 2005; Van Vugt et al., 2006; Germano et al., 2007). As a leptin-regulated neurotransmitter, the expression of CART mRNA and peptide levels at the Arc is described to be positively correlated with circulating leptin levels (Kristensen et al., 1998; Ahima et al., 1999; Ahima and Hileman, 2000; Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004). This relationship between leptin and CART levels was less consistently demonstrated at the PVN and LHA (Wortley et al., 2004), despite evidence supporting a pivotal role of CART-containing neurons projecting from the Arc to the second order neurons located in the PVN and LHA in producing anorexia (Elias et al., 1999; Wang et al., 2000; Fekete et al., 2004). Intravenous leptin administration was shown to induce Fos expression in hypothalamic CART neurons in the PVN, DMH, Arc, and the ventral premammillary nucleus (Elias et al., 1998, 2001). Whilst Arc CART mRNA and peptide levels were strongly downregulated in food-deprived animals, the transcripts were nearly absent in genetically obese fa/fa rats and ob/ob mice with disrupted leptin signaling, wherein daily intraperitoneal leptin treatment led to CART restoration in the Arc and DMH (Friedman and Halaas, 1998; Kristensen et al., 1998; Ahima et al., 1999; Ahima and Hileman, 2000; Rohner-Jeanrenaud et al., 2002), suggesting that leptin-induced anorexigenic actions may be mediated via CART neurons at the Arc. In comparison, in the anx/anx anorexia mouse model characterized by marked reduction in feeding and premature death, CART expression was significantly lower in the Arc, and less prominently in the DMH and LHA regions (Johansen et al., 2000). The reduced Arc CART expression, together with downregulated serum leptin levels, was attributed to a compensatory response to the energy-deprived state, as well as a probable molecular defect in the Arc deregulating the cellular source of CART mRNA (Johansen et al., 2000). In contrast with genetically obese animal models, diet-induced obese (DIO) rodents subjected to a high fat diet (HFD) have been shown to display higher Arc CART mRNA levels compared with lean animals fed a low fat diet, due to hyperleptinaemia (Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004; Hou et al., 2010). Elevated CART transcript levels were also found in normal-weight obesity-prone rats compared to obesity-resistant subjects, where the Arc leptin-CART pathway was proposed to respond to fat-rich dietary intervention through inhibiting excessive body fat accrual by substituting lipid storage with lipid mobilization (Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004)."}

{"project":"0_colil","denotations":[{"id":"25352770-9590691-357417","span":{"begin":672,"end":676},"obj":"9590691"},{"id":"25352770-9661247-357418","span":{"begin":694,"end":698},"obj":"9661247"},{"id":"25352770-10612705-357419","span":{"begin":714,"end":718},"obj":"10612705"},{"id":"25352770-10650962-357421","span":{"begin":741,"end":745},"obj":"10650962"},{"id":"25352770-11684040-357422","span":{"begin":761,"end":765},"obj":"11684040"},{"id":"25352770-11959420-357423","span":{"begin":778,"end":782},"obj":"11959420"},{"id":"25352770-15659233-357424","span":{"begin":800,"end":804},"obj":"15659233"},{"id":"25352770-17124379-357425","span":{"begin":823,"end":827},"obj":"17124379"},{"id":"25352770-17669377-357426","span":{"begin":845,"end":849},"obj":"17669377"},{"id":"25352770-9590691-357427","span":{"begin":1042,"end":1046},"obj":"9590691"},{"id":"25352770-10537115-357428","span":{"begin":1062,"end":1066},"obj":"10537115"},{"id":"25352770-11024558-357429","span":{"begin":1087,"end":1091},"obj":"11024558"},{"id":"25352770-11850744-357430","span":{"begin":1119,"end":1123},"obj":"11850744"},{"id":"25352770-14700744-357431","span":{"begin":1141,"end":1145},"obj":"14700744"},{"id":"25352770-14700744-357432","span":{"begin":1268,"end":1272},"obj":"14700744"},{"id":"25352770-10482243-357433","span":{"begin":1461,"end":1465},"obj":"10482243"},{"id":"25352770-11043558-357434","span":{"begin":1480,"end":1484},"obj":"11043558"},{"id":"25352770-14730586-357435","span":{"begin":1501,"end":1505},"obj":"14730586"},{"id":"25352770-9883730-357436","span":{"begin":1681,"end":1685},"obj":"9883730"},{"id":"25352770-11241374-357437","span":{"begin":1687,"end":1691},"obj":"11241374"},{"id":"25352770-9796811-357438","span":{"begin":2015,"end":2019},"obj":"9796811"},{"id":"25352770-9590691-357439","span":{"begin":2040,"end":2044},"obj":"9590691"},{"id":"25352770-10537115-357440","span":{"begin":2060,"end":2064},"obj":"10537115"},{"id":"25352770-11024558-357441","span":{"begin":2085,"end":2089},"obj":"11024558"},{"id":"25352770-11850744-357442","span":{"begin":2117,"end":2121},"obj":"11850744"},{"id":"25352770-11113536-357443","span":{"begin":2456,"end":2460},"obj":"11113536"},{"id":"25352770-11113536-357444","span":{"begin":2731,"end":2735},"obj":"11113536"},{"id":"25352770-11850744-357445","span":{"begin":3009,"end":3013},"obj":"11850744"},{"id":"25352770-14700744-357446","span":{"begin":3031,"end":3035},"obj":"14700744"},{"id":"25352770-20626417-357447","span":{"begin":3049,"end":3053},"obj":"20626417"},{"id":"25352770-11850744-357448","span":{"begin":3398,"end":3402},"obj":"11850744"},{"id":"25352770-14700744-357449","span":{"begin":3420,"end":3424},"obj":"14700744"}],"text":"While the role of CART in controlling appetite and energy homeostasis in the human system might be somewhat different, in rodents, the neuronal network in which CART is involved to modulate energy homeostasis has been well-described. The expression of endogenous CART at brain regions involved in feeding regulation has been shown to be sensitive to the energy balance status and the genetic background of mice. In brief, fasting has been documented in various mammals to reduce CART mRNA levels at the hypothalamic PVN, Arc, perifornical region, as well as the nucleus accumbens shell (AcbSh) of the striatum, whilst refeeding restored the expression (Kristensen et al., 1998; Lambert et al., 1998; Adams et al., 1999; Vrang et al., 1999a, 2000; Henry et al., 2001; Li et al., 2002; Yang and Shieh, 2005; Van Vugt et al., 2006; Germano et al., 2007). As a leptin-regulated neurotransmitter, the expression of CART mRNA and peptide levels at the Arc is described to be positively correlated with circulating leptin levels (Kristensen et al., 1998; Ahima et al., 1999; Ahima and Hileman, 2000; Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004). This relationship between leptin and CART levels was less consistently demonstrated at the PVN and LHA (Wortley et al., 2004), despite evidence supporting a pivotal role of CART-containing neurons projecting from the Arc to the second order neurons located in the PVN and LHA in producing anorexia (Elias et al., 1999; Wang et al., 2000; Fekete et al., 2004). Intravenous leptin administration was shown to induce Fos expression in hypothalamic CART neurons in the PVN, DMH, Arc, and the ventral premammillary nucleus (Elias et al., 1998, 2001). Whilst Arc CART mRNA and peptide levels were strongly downregulated in food-deprived animals, the transcripts were nearly absent in genetically obese fa/fa rats and ob/ob mice with disrupted leptin signaling, wherein daily intraperitoneal leptin treatment led to CART restoration in the Arc and DMH (Friedman and Halaas, 1998; Kristensen et al., 1998; Ahima et al., 1999; Ahima and Hileman, 2000; Rohner-Jeanrenaud et al., 2002), suggesting that leptin-induced anorexigenic actions may be mediated via CART neurons at the Arc. In comparison, in the anx/anx anorexia mouse model characterized by marked reduction in feeding and premature death, CART expression was significantly lower in the Arc, and less prominently in the DMH and LHA regions (Johansen et al., 2000). The reduced Arc CART expression, together with downregulated serum leptin levels, was attributed to a compensatory response to the energy-deprived state, as well as a probable molecular defect in the Arc deregulating the cellular source of CART mRNA (Johansen et al., 2000). In contrast with genetically obese animal models, diet-induced obese (DIO) rodents subjected to a high fat diet (HFD) have been shown to display higher Arc CART mRNA levels compared with lean animals fed a low fat diet, due to hyperleptinaemia (Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004; Hou et al., 2010). Elevated CART transcript levels were also found in normal-weight obesity-prone rats compared to obesity-resistant subjects, where the Arc leptin-CART pathway was proposed to respond to fat-rich dietary intervention through inhibiting excessive body fat accrual by substituting lipid storage with lipid mobilization (Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004)."}

{"project":"2_test","denotations":[{"id":"25352770-9590691-38284406","span":{"begin":672,"end":676},"obj":"9590691"},{"id":"25352770-9661247-38284407","span":{"begin":694,"end":698},"obj":"9661247"},{"id":"25352770-10612705-38284408","span":{"begin":714,"end":718},"obj":"10612705"},{"id":"25352770-10650962-38284410","span":{"begin":741,"end":745},"obj":"10650962"},{"id":"25352770-11684040-38284411","span":{"begin":761,"end":765},"obj":"11684040"},{"id":"25352770-11959420-38284412","span":{"begin":778,"end":782},"obj":"11959420"},{"id":"25352770-15659233-38284413","span":{"begin":800,"end":804},"obj":"15659233"},{"id":"25352770-17124379-38284414","span":{"begin":823,"end":827},"obj":"17124379"},{"id":"25352770-17669377-38284415","span":{"begin":845,"end":849},"obj":"17669377"},{"id":"25352770-9590691-38284416","span":{"begin":1042,"end":1046},"obj":"9590691"},{"id":"25352770-10537115-38284417","span":{"begin":1062,"end":1066},"obj":"10537115"},{"id":"25352770-11024558-38284418","span":{"begin":1087,"end":1091},"obj":"11024558"},{"id":"25352770-11850744-38284419","span":{"begin":1119,"end":1123},"obj":"11850744"},{"id":"25352770-14700744-38284420","span":{"begin":1141,"end":1145},"obj":"14700744"},{"id":"25352770-14700744-38284421","span":{"begin":1268,"end":1272},"obj":"14700744"},{"id":"25352770-10482243-38284422","span":{"begin":1461,"end":1465},"obj":"10482243"},{"id":"25352770-11043558-38284423","span":{"begin":1480,"end":1484},"obj":"11043558"},{"id":"25352770-14730586-38284424","span":{"begin":1501,"end":1505},"obj":"14730586"},{"id":"25352770-9883730-38284425","span":{"begin":1681,"end":1685},"obj":"9883730"},{"id":"25352770-11241374-38284426","span":{"begin":1687,"end":1691},"obj":"11241374"},{"id":"25352770-9796811-38284427","span":{"begin":2015,"end":2019},"obj":"9796811"},{"id":"25352770-9590691-38284428","span":{"begin":2040,"end":2044},"obj":"9590691"},{"id":"25352770-10537115-38284429","span":{"begin":2060,"end":2064},"obj":"10537115"},{"id":"25352770-11024558-38284430","span":{"begin":2085,"end":2089},"obj":"11024558"},{"id":"25352770-11850744-38284431","span":{"begin":2117,"end":2121},"obj":"11850744"},{"id":"25352770-11113536-38284432","span":{"begin":2456,"end":2460},"obj":"11113536"},{"id":"25352770-11113536-38284433","span":{"begin":2731,"end":2735},"obj":"11113536"},{"id":"25352770-11850744-38284434","span":{"begin":3009,"end":3013},"obj":"11850744"},{"id":"25352770-14700744-38284435","span":{"begin":3031,"end":3035},"obj":"14700744"},{"id":"25352770-20626417-38284436","span":{"begin":3049,"end":3053},"obj":"20626417"},{"id":"25352770-11850744-38284437","span":{"begin":3398,"end":3402},"obj":"11850744"},{"id":"25352770-14700744-38284438","span":{"begin":3420,"end":3424},"obj":"14700744"}],"text":"While the role of CART in controlling appetite and energy homeostasis in the human system might be somewhat different, in rodents, the neuronal network in which CART is involved to modulate energy homeostasis has been well-described. The expression of endogenous CART at brain regions involved in feeding regulation has been shown to be sensitive to the energy balance status and the genetic background of mice. In brief, fasting has been documented in various mammals to reduce CART mRNA levels at the hypothalamic PVN, Arc, perifornical region, as well as the nucleus accumbens shell (AcbSh) of the striatum, whilst refeeding restored the expression (Kristensen et al., 1998; Lambert et al., 1998; Adams et al., 1999; Vrang et al., 1999a, 2000; Henry et al., 2001; Li et al., 2002; Yang and Shieh, 2005; Van Vugt et al., 2006; Germano et al., 2007). As a leptin-regulated neurotransmitter, the expression of CART mRNA and peptide levels at the Arc is described to be positively correlated with circulating leptin levels (Kristensen et al., 1998; Ahima et al., 1999; Ahima and Hileman, 2000; Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004). This relationship between leptin and CART levels was less consistently demonstrated at the PVN and LHA (Wortley et al., 2004), despite evidence supporting a pivotal role of CART-containing neurons projecting from the Arc to the second order neurons located in the PVN and LHA in producing anorexia (Elias et al., 1999; Wang et al., 2000; Fekete et al., 2004). Intravenous leptin administration was shown to induce Fos expression in hypothalamic CART neurons in the PVN, DMH, Arc, and the ventral premammillary nucleus (Elias et al., 1998, 2001). Whilst Arc CART mRNA and peptide levels were strongly downregulated in food-deprived animals, the transcripts were nearly absent in genetically obese fa/fa rats and ob/ob mice with disrupted leptin signaling, wherein daily intraperitoneal leptin treatment led to CART restoration in the Arc and DMH (Friedman and Halaas, 1998; Kristensen et al., 1998; Ahima et al., 1999; Ahima and Hileman, 2000; Rohner-Jeanrenaud et al., 2002), suggesting that leptin-induced anorexigenic actions may be mediated via CART neurons at the Arc. In comparison, in the anx/anx anorexia mouse model characterized by marked reduction in feeding and premature death, CART expression was significantly lower in the Arc, and less prominently in the DMH and LHA regions (Johansen et al., 2000). The reduced Arc CART expression, together with downregulated serum leptin levels, was attributed to a compensatory response to the energy-deprived state, as well as a probable molecular defect in the Arc deregulating the cellular source of CART mRNA (Johansen et al., 2000). In contrast with genetically obese animal models, diet-induced obese (DIO) rodents subjected to a high fat diet (HFD) have been shown to display higher Arc CART mRNA levels compared with lean animals fed a low fat diet, due to hyperleptinaemia (Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004; Hou et al., 2010). Elevated CART transcript levels were also found in normal-weight obesity-prone rats compared to obesity-resistant subjects, where the Arc leptin-CART pathway was proposed to respond to fat-rich dietary intervention through inhibiting excessive body fat accrual by substituting lipid storage with lipid mobilization (Rohner-Jeanrenaud et al., 2002; Wortley et al., 2004)."}