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James R Paterniti

Publications and source records attributed to James R Paterniti.

6 recordsLinked to original sources
PubMed2005

Human apoA-I expression in CETP transgenic rats leads to lower levels of apoC-I in HDL and to magnification of CETP-mediated lipoprotein changes.

Plasma cholesteryl ester transfer protein (CETP) has a profound effect on neutral lipid transfers between HDLs and apolipoprotein B (apoB)-containing lipoproteins when it is expressed in combination with human apoA-I in HuAI/CETP transgenic (Tg) rodents. In the present study, human apoA-I-mediated lipoprotein changes in HuAI/CETPTg rats are characterized by 3- to 5-fold increments in the apoB-containing lipoprotein-to-HDL cholesterol ratio, and in the cholesteryl ester-to-triglyceride ratio in apoB-containing lipoproteins. These changes occur despite no change in plasma CETP concentration in HuAI/CETPTg rats, as compared with CETPTg rats. A number of HDL apolipoproteins, including rat apoA-I and rat apoC-I are removed from the HDL surface as a result of human apoA-I overexpression. Rat apoC-I, which is known to constitute a potent inhibitor of CETP, accounts for approximately two-thirds of CETP inhibitory activity in HDL from wild-type rats, and the remainder is carried by other HDL-bound apolipoprotein inhibitors. It is concluded that human apoA-I overexpression modifies HDL particles in a way that suppresses their ability to inhibit CETP. An apoC-I decrease in HDL of HuAI/CETPTg rats contributes chiefly to the loss of the CETP-inhibitory potential that is normally associated with wild-type HDL.

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PubMed2004

Effects of peptide YY[3-36] on short-term food intake in mice are not affected by prevailing plasma ghrelin levels.

The gut-derived hormones peptide YY[3-36] (PYY[3-36]) and ghrelin are believed to influence similar hypothalamic circuits, albeit with opposing actions on energy balance. Thus, we carried out a series of studies to evaluate the interaction of these hormones on short-term food intake responses in mice. Intraperitoneal PYY[3-36] injection reduced short-term food intake by up to 50% in overnight-fasted mice and in postabsorptive animals during the early and late light cycle. This effect was not sensitive to the prevailing endogenous plasma acyl-ghrelin concentrations, which ranged from high physiological (overnight-fasted, 1252 +/- 108 pg/ml) to low levels (late light cycle, 402 +/- 33 pg/ml). PYY[3-36] administration did not reduce plasma total or acyl-ghrelin concentration in conjunction with its anorexigenic actions. Ghrelin increased short-term food intake by up to 1.8-fold in mice treated ip in the early light cycle, but was ineffective in animals treated after an overnight fast or during the late light cycle. Ghrelin did not increase food intake or GH secretion unless plasma levels were increased above high physiological fasting values. The anorexigenic effect of PYY[3-36] over a range of doses was not compromised by coinjection of ghrelin, and PYY[3-36] reduced food intake in agouti mice, which lack fully functional melanocortin signaling. These results in mice support a model in which 1) PYY[3-36] diminishes short-term food intake at least in part through mechanisms distinct from the neuropeptide Y/proopiomelanocortin neural circuits engaged by ghrelin; and 2) a reduction in circulating ghrelin is not requisite for the anorexigenic effects of PYY[3-36].

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PubMed2002

Thiourea-based gemfibrozil analogues as HDL-elevating agents.

A series of gemfibrozil analogues with a thiourea moiety embedded in the side chain was prepared and evaluated as HDL-elevating agents. Derivatives 8b, 9b, 9c, and 9d were found to be approximately as effective as gemfibrozil (1) for HDL cholesterol elevation.

Administration, Oral↗
PubMed2002

A tailored therapy for the metabolic syndrome: the dual peroxisome proliferator-activated receptor-alpha/gamma agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models.

A novel nonthiazolidinedione dual peroxisome proliferator- activated receptor (PPAR)-alpha/gamma agonist, LY465608, was designed to address the major metabolic disturbances of type 2 diabetes. LY465608 altered PPAR-responsive genes in liver and fat of db/db mice and dose-dependently lowered plasma glucose in hyperglycemic male Zucker diabetic fatty (ZDF) rats, with an ED(50) for glucose normalization of 3.8 mg small middle dot kg(-1) small middle dot day(-1). Metabolic improvements were associated with enhanced insulin sensitivity, as demonstrated in female obese Zucker (fa/fa) rats using both oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. Further characterization of LY465608 revealed metabolic changes distinct from a selective PPAR-gamma agonist, which were presumably due to the concomitant PPAR-alpha agonism, lower respiratory quotient, and less fat accumulation, despite a similar impact on glycemia in male ZDF rats. In addition to these alterations in diabetic and insulin-resistant animals, LY465608 dose-dependently elevated HDL cholesterol and lowered plasma triglycerides in human apolipoprotein A-I transgenic mice, demonstrating that this compound significantly improves primary cardiovascular risk factors. Overall, these studies demonstrate that LY465608 beneficially impacts multiple facets of type 2 diabetes and associated cardiovascular risk, including those facets involved in the development of micro- and macrovascular complications, which are the major sources for morbidity and mortality in these patients.

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