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In vitro inhibition of adipocyte lipogenesis in adipocytes exposed to serum from obese hyperleptinemic rats.
ARTICLE IN PRESS Abstracts / Appetite 49 (2007) 272–341
In vitro inhibition of adipocyte lipogenesis in adipocytes exposed to serum from obese hyperleptinemic rats E.W. KELSO,
R.B.S. HARRIS. Department of Foods and Nutrition, University of Georgia, Athens, GA 30602, USA Parabiosis studies between obese overfed rats and ad libitumfed rats demonstrated the presence of a circulating factor produced by the obese rats that reduced body fat in the ad libitum partner by inhibiting lipogenic pathways. Subsequent in vitro studies showed that de novo lipogenesis was inhibited in adipocytes incubated for 12 h in the media containing 2% by volume serum from overfed obese rats. When leptin was discovered it was assumed that this was the ‘‘anti-lipogenic’’ factor (ALF) present in the serum from obese animals. Recently we have found that leptin does not inhibit lipogenesis in adipocytes in vitro. Since ALF is not present in serum from obese Zucker rats it appears that leptin is required for release of ALF. We have recently used malic enzyme activity as a measure of lipogenesis and find that serum from overfed obese rats inhibits enzyme activity in adipocytes but leptin alone (100 ng/ml) and serum from leptin-infused rats do not. Consistent with this observation, malic enzyme activity is not substantially reduced in adipose tissue from leptin-infused rats even though lipid synthesis is inhibited. We hypothesize that in conditions of obesity, leptin induces the release of a circulating factor that inhibits lipogenesis in mature adipocytes. The function of this factor is undefined, but it may influence the accumulation of lipid in different fat depots or it may prevent enlarged adipocytes from becoming unstable. Supported by Grant R01DK53903 awarded to RBSH. 10.1016/j.appet.2007.03.105
Interaction of MMP-3 and sex hormones in the control of energy balance C.J. KEMP, J. CALDWELL-LAWSON,
D.J. CLEGG, S.C. BENOIT. Department of Psychiatry, Obesity Research Center, University of Cincinnati, Cincinnati, OH, USA Matrix metalloproteinase-3 (MMP-3) is an endopeptidase important for regulating cell-to-cell interactions and remodeling the extracellular matrix, including the development of adipose tissue. We hypothesized that MMP-3 is also active in the central nervous system, specifically acting to cleave synedecan-3 and thereby regulate AgRP signaling. Because previous studies have shown sex difference in syndecan-3-mediated regulation of food intake, we also tested the hypothesis that CNS MMP-3 might mediate the sex-differences underlying syndecan-3 regulation of energy balance. We first observed that MMP-3 deficient mice are hyperphagic and gain significantly more weight on high-fat diet compared to wild-type controls. Second, MMP-3 null mice exhibit a delayed and prolonged orexigenic response to ICV NPY and AgRP, compared to wild-type controls. These findings are consistent with our hypothesis that MMP-3 regulates cleavage of cell-surface syndecan-3. To test the role of sex hormones in mice lacking MMP-3, we assessed food intake following ovariectomy (OVX). WT-ovariectomized mice exhibit hyperpha-
303
gia and increased food intake and body weight compared to sham-controls. A separate cohort of MMP-3 null or WT female mice was randomized to receive OVX or sham surgery, after which we recorded daily food intake and body weights. While MMP-3 null and WT OVX mice exhibited similar amounts of hyperphagia, MMP-3 KO mice gained more weight than WT controls. Collectively, these data suggest an important role for MMP-3 in the regulation of food intake and the mediation of sexhormones on energy balance, consistent with a potential role to regulate cleavage of hypothalamic syndecans. 10.1016/j.appet.2007.03.106
Ginsenoside Rb1 as a suppressor in central modulation of feeding in the rat J.H. KIMa, H.Y. JOUNGb, S.A. KANGc,
K.H. PYUNb, I. SHIMb. aImmunology and Cell Biology Core Laboratory, Catholic Research Institute of Medical Science, The Catholic University, Seoul, Republic of Korea. b Department of Integrative Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. c Department of Fermented Food Science, Seoul University of Venture & Information, Seoul, Republic of Korea Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. In the present study, the effects of ginsenoside Rb1 on feeding behavior and endogenous chemical substances were investigated in the normal (N) diet and high-fat (HF) diet rats. The male 4-week-old SD rats were randomly divided into N diet and HF diet group. After 5 weeks, each group was subdivided into N diet-Rb1 and HF diet-Rb1 group. The anti-obesity effects of Rb1 were estimated through analyses of changes in body weight, food intake, body fat mass, serum leptin, serum nitric oxide (NO), and hypothalamic appetitive peptides (neuropeptide Y:NPY, cholecystokinin:CCK), and locomotor activity. Administration of Rb1 (10 mg/kg, i.p., 3 weeks) in the HF diet group reduced the body weight, total food intake, fat contents, serum leptin and NO to level equals or below the N diet group. In the hypothalamus, especially paraventricular nucleus, the expression of orexigenic NPY was decreased and the expression of anorexigenic CCK was increased by Rb1 treatment compared with that of the HF diet group. Rb1-treated group in the HF diet from 1 week after treatment increased locomotor activity relative to HF diet group, but significant difference was not found among groups for the other experimental periods. The Rb1 may be useful agent for the control obesity via the implication in the peripheral and central appetitive modulators. 10.1016/j.appet.2007.03.107
In vitro inhibition of adipocyte lipogenesis in adipocytes exposed to serum from obese hyperleptinemic rats E.W. KELSO,
R.B.S. HARRIS. Department of Foods and Nutrition, University of Georgia, Athens, GA 30602, USA Parabiosis studies between obese overfed rats and ad libitumfed rats demonstrated the presence of a circulating factor produced by the obese rats that reduced body fat in the ad libitum partner by inhibiting lipogenic pathways. Subsequent in vitro studies showed that de novo lipogenesis was inhibited in adipocytes incubated for 12 h in the media containing 2% by volume serum from overfed obese rats. When leptin was discovered it was assumed that this was the ‘‘anti-lipogenic’’ factor (ALF) present in the serum from obese animals. Recently we have found that leptin does not inhibit lipogenesis in adipocytes in vitro. Since ALF is not present in serum from obese Zucker rats it appears that leptin is required for release of ALF. We have recently used malic enzyme activity as a measure of lipogenesis and find that serum from overfed obese rats inhibits enzyme activity in adipocytes but leptin alone (100 ng/ml) and serum from leptin-infused rats do not. Consistent with this observation, malic enzyme activity is not substantially reduced in adipose tissue from leptin-infused rats even though lipid synthesis is inhibited. We hypothesize that in conditions of obesity, leptin induces the release of a circulating factor that inhibits lipogenesis in mature adipocytes. The function of this factor is undefined, but it may influence the accumulation of lipid in different fat depots or it may prevent enlarged adipocytes from becoming unstable. Supported by Grant R01DK53903 awarded to RBSH. 10.1016/j.appet.2007.03.105
Interaction of MMP-3 and sex hormones in the control of energy balance C.J. KEMP, J. CALDWELL-LAWSON,
D.J. CLEGG, S.C. BENOIT. Department of Psychiatry, Obesity Research Center, University of Cincinnati, Cincinnati, OH, USA Matrix metalloproteinase-3 (MMP-3) is an endopeptidase important for regulating cell-to-cell interactions and remodeling the extracellular matrix, including the development of adipose tissue. We hypothesized that MMP-3 is also active in the central nervous system, specifically acting to cleave synedecan-3 and thereby regulate AgRP signaling. Because previous studies have shown sex difference in syndecan-3-mediated regulation of food intake, we also tested the hypothesis that CNS MMP-3 might mediate the sex-differences underlying syndecan-3 regulation of energy balance. We first observed that MMP-3 deficient mice are hyperphagic and gain significantly more weight on high-fat diet compared to wild-type controls. Second, MMP-3 null mice exhibit a delayed and prolonged orexigenic response to ICV NPY and AgRP, compared to wild-type controls. These findings are consistent with our hypothesis that MMP-3 regulates cleavage of cell-surface syndecan-3. To test the role of sex hormones in mice lacking MMP-3, we assessed food intake following ovariectomy (OVX). WT-ovariectomized mice exhibit hyperpha-
303
gia and increased food intake and body weight compared to sham-controls. A separate cohort of MMP-3 null or WT female mice was randomized to receive OVX or sham surgery, after which we recorded daily food intake and body weights. While MMP-3 null and WT OVX mice exhibited similar amounts of hyperphagia, MMP-3 KO mice gained more weight than WT controls. Collectively, these data suggest an important role for MMP-3 in the regulation of food intake and the mediation of sexhormones on energy balance, consistent with a potential role to regulate cleavage of hypothalamic syndecans. 10.1016/j.appet.2007.03.106
Ginsenoside Rb1 as a suppressor in central modulation of feeding in the rat J.H. KIMa, H.Y. JOUNGb, S.A. KANGc,
K.H. PYUNb, I. SHIMb. aImmunology and Cell Biology Core Laboratory, Catholic Research Institute of Medical Science, The Catholic University, Seoul, Republic of Korea. b Department of Integrative Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. c Department of Fermented Food Science, Seoul University of Venture & Information, Seoul, Republic of Korea Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. In the present study, the effects of ginsenoside Rb1 on feeding behavior and endogenous chemical substances were investigated in the normal (N) diet and high-fat (HF) diet rats. The male 4-week-old SD rats were randomly divided into N diet and HF diet group. After 5 weeks, each group was subdivided into N diet-Rb1 and HF diet-Rb1 group. The anti-obesity effects of Rb1 were estimated through analyses of changes in body weight, food intake, body fat mass, serum leptin, serum nitric oxide (NO), and hypothalamic appetitive peptides (neuropeptide Y:NPY, cholecystokinin:CCK), and locomotor activity. Administration of Rb1 (10 mg/kg, i.p., 3 weeks) in the HF diet group reduced the body weight, total food intake, fat contents, serum leptin and NO to level equals or below the N diet group. In the hypothalamus, especially paraventricular nucleus, the expression of orexigenic NPY was decreased and the expression of anorexigenic CCK was increased by Rb1 treatment compared with that of the HF diet group. Rb1-treated group in the HF diet from 1 week after treatment increased locomotor activity relative to HF diet group, but significant difference was not found among groups for the other experimental periods. The Rb1 may be useful agent for the control obesity via the implication in the peripheral and central appetitive modulators. 10.1016/j.appet.2007.03.107