American journal of physiology. Endocrinology and metabolism
-
Am. J. Physiol. Endocrinol. Metab. · Jan 2011
Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats.
Central obesity is associated with low-grade inflammation that promotes type 2 diabetes and cardiovascular disease in obese individuals. The 12- and 5-lipoxygenase (12-LO and 5-LO) enzymes have been linked to inflammatory changes, leading to the development of atherosclerosis. 12-LO has also been linked recently to inflammation and insulin resistance in adipocytes. We analyzed the expression of LO and proinflammatory cytokines in adipose tissue and adipocytes in obese Zucker rats, a widely studied genetic model of obesity, insulin resistance, and the metabolic syndrome. mRNA expression of 12-LO, 5-LO, and 5-LO-activating protein (FLAP) was upregulated in adipocytes and adipose tissue from obese Zucker rats compared with those from lean rats. ⋯ LSF also reduced p-STAT4 in visceral adipose tissue from obese Zucker rats and improved the metabolic profile, reducing fasting plasma glucose and increasing insulin sensitivity in obese Zucker rats. In 3T3-L1 adipocytes, LSF abrogated the inflammatory response induced by LO products. Thus, therapeutic agents reducing LO or STAT4 activation may provide novel tools to reduce obesity-induced inflammation.
-
Am. J. Physiol. Endocrinol. Metab. · Dec 2010
Randomized Controlled TrialEffects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects.
We compared the effects of high and low oral and intravenous (iv) fat load on blood pressure (BP), endothelial function, autonomic nervous system, and oxidative stress in obese healthy subjects. Thirteen obese subjects randomly received five 8-h infusions of iv saline, 20 (32 g, low iv fat) or 40 ml/h intralipid (64 g, high iv fat), and oral fat load at 32 (low oral) or 64 g (high oral). Systolic BP increased by 14 ± 10 (P = 0.007) and 12 ± 9 mmHg (P = 0.007) after low and high iv lipid infusions and by 13 ± 17 (P = 0.045) and 11 ± 11 mmHg (P = 0.040) after low and high oral fat loads, respectively. ⋯ Intravenous saline and both oral and iv fat load reduced leptin concentration from baseline (P < 0.01). In conclusion, acute fat load administered orally or intravenously significantly increased blood pressure, altered endothelial function, and activated sympathetic nervous system by mechanisms not likely depending on changes in leptin, glucose, and insulin levels in obese healthy subjects. Thus, fat load, independent of its source, has deleterious hemodynamic effects in obese subjects.
-
Am. J. Physiol. Endocrinol. Metab. · Sep 2010
Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus.
Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 are derived from distinct regions of VGF, a neurosecretory protein. Vgf(-/-) mice exhibit dwarfism and hypermetabolic rates, suggesting that VGF or VGF-derived peptides play important roles in energy metabolism. Here, we examined the role of NERPs in the central regulation of feeding and energy homeostasis. ⋯ NERP-2 did not induce food intake or locomotor activity in orexin-deficient mice. Our findings indicate that hypothalamic NERP-2 plays a role in the control of food intake and energy homeostasis via the orexin pathway. Thus, VGF serves as a precursor of multiple bioactive peptides exerting a diverse set of neuroendocrine functions.
-
Am. J. Physiol. Endocrinol. Metab. · Jun 2010
Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine.
Sepsis and lipopolysaccharide (LPS) may decrease skeletal muscle protein synthesis by impairing mTOR (mammalian target of rapamycin) activity. The role of mTOR in regulating muscle protein synthesis was assessed in wild-type (WT) and mTOR heterozygous (+/-) mice under basal conditions and in response to LPS and/or leucine stimulation. No difference in body weight of mTOR(+/-) mice was observed compared with WT mice; whereas whole body lean body mass was reduced. ⋯ Plasma insulin and IGF-I as well as tissue expression of TNFalpha, IL-6, or NOS2 did not differ between WT and mTOR(+/-) mice. Finally, whereas LPS impaired the ability of leucine to stimulate muscle protein synthesis and 4E-BP1 phosphorylation in WT mice, this inflammatory state rendered mTOR(+/-) mice leucine unresponsive. These data support the idea that the LPS-induced reduction in mTOR activity is relatively more important in regulating skeletal muscle mass in response to nutrient stimulation than under basal conditions.