Glucose and lipid metabolism alterations in liver and adipose tissue pre-dispose p47^phox knockout mice to systemic insulin resistance

Abstract

Oxidative stress due to enhanced production or reduced scavenging of reactive oxygen species (ROS) has been associated with diet (dyslipidemia) induced obesity and insulin resistance (IR). The present study was undertaken to assess the role of p47 in IR using wild type (WT) and p47 mice, fed with different diets (HFD, LFD or Chow). Augmented body weight, glucose intolerance and reduced insulin sensitivity were observed in p47 mice fed with 45% HFD and 10% LFD. Further, body fat and circulating lipids were increased significantly with 5 weeks LFD feeding in p47 mice, while parameters of energy homeostasis were reduced as compared with WT mice. LFD fed knockout (KO) mice showed an enhanced hepatic glycogenolysis, and reduced insulin signalling in liver and adipose tissue, while skeletal muscle tissue remained unaffected. A significant increase in hepatic lipids, adiposity, as well as expression of genes regulating lipid synthesis, breakdown and efflux were observed in LFD fed p47 mice after 5 weeks. On the other hand, mice lacking p47 demonstrated altered glucose tolerance and tissue insulin sensitivity after 5 weeks chow feeding, while changes in body weight, respiratory exchange ratio (RER) and heat production are non-significant. Our data demonstrate that lack of p47 is sufficient to induce IR through altered glucose and lipid utilization by the liver and adipose tissue.

Vancomycin-Induced Modulation of Gram-Positive Gut Bacteria And Metabolites Remediate Insulin Resistance In INOS Knockout Mice

“…Quantitative gene expression analysis was performed using SYBR Green as described previously [37]. Brie y, total RNA was extracted using TRIZOL reagent followed by cDNA synthesis using RevertAid rst strand cDNA synthesis kit using manufacturer's protocol.…”

“…Body composition (fat and lean mass) was analyzed in live, conscious mice by echo MRI (E26-226-RM Echo MRI LLC, USA) allowing limited horizontal and vertical movements by applying radio frequency pulses at a distinct static magnetic eld [37].…”

Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait

“…Several proteins involved in mitochondrial β-oxidation (HADHA, ACADVL, ACADL, ECH1, ECHS1), which generates acetyl-CoA to feed the TCA cycle, and peroxisome β-oxidation (ECH1, ACOX1), major fatty acids degradative pathway, are upregulated in GDE by HD, suggesting that fatty acids are favoured as energy source over glucose (Figure 5). In addition, over-activation of lipid metabolism related pathways is a common feature of obesity and T2D, leading to a state of hyperglycemia [34; 35; 36]. Moreover, a family of acyl-CoA thioesterases (ACOTs) were particularly upregulated; these are intermediaries in the decision whether fatty acids are directed to the TCA cycle or stored, (Figure 5, Supplementary Figure 4) [37; 38].…”

Systemic Insulin Resistance and Metabolic Perturbations in Chow Fed Inducible Nitric Oxide Synthase Knockout Male Mice: Partial Reversal by Nitrite Supplementation

“…Conscious, unrestrained mice were individually placed in the Oxymax CLAMS (Columbus Instruments, Columbus, OH, USA) with free access to food and water for metabolic measurements [ 45 ]. After pre-calibration of system and animal acclimatization, oxygen consumption (VO 2 , mL/kg/h), carbon dioxide produced (VCO 2 , mL/kg/h) along with food and water intake, RER (VCO 2 /VO 2 , m/kg/min), metabolic rates (BMR and RMR) and energy expenditure (kcal/h; heat production) were determined over a 3 day period.…”

“…Formalin fixed and, paraffin embedded adipose tissue (eWAT) was sectioned into 5 μm thin serial slices and HE stained for morphological examination [ 45 ]. Adipocytes area was calculated using Adiposoft plugin in Fiji software for Windows 64bit (NIH, Bethesda, MA, USA).…”