Effects of intravenous glucose and lipids on innate immune cell activation in healthy, obese, and type 2 diabetic subjects

Abstract

Atherosclerosis/cardiovascular disease are major causes of morbidity/mortality in obesity and type 2 diabetes (T2D), and have been associated with activation of innate immune cells, their diapedesis to the arterial intima and formation of the atherosclerotic plaque. While in obesity/T2D immune cell activation likely depends on dysregulated metabolism, the interaction between individual metabolic factors typical of these conditions (hyperglycemia, hyperlipidemia), innate immune cell activation, and the progression of atherosclerosis remains unclear. We, therefore, measured by flow cytometry cell surface expression of CD11b, CD14, CD16, CD62L, and CD66b, known markers of granulocyte (Gc) and monocyte (Mc) activation, in five healthy, five obese, and five T2D subjects, during 4-h i.v. infusions of 20% dextrose (raising blood sugar levels to ∼220 mg/dL), 20% Intralipid (raising trygliceride levels to ∼6 mmol/L), or a combination of the two. We hypothesized that both glucose and lipids would increase Gc/Mc surface marker expression, and simultaneous infusion would have an additive or synergistic effect. Surprisingly, though, infusion of glucose alone had little effect, while lipids, alone or combined with glucose, significantly increased expression of several markers (such as CD11b in Gc and Mc, and CD66 b in GC) within 60–90 min. Less pronounced increases in systemic inflammatory cytokines also occurred in obese and T2D subject, with no acute changes in gene expression of the the proinflammatory genes NFκB and CCR2. Our results suggest that lipids may be stronger acute contributors to innate cell activation than acute hyperglycemia per se, possibly helping shape more effective preventive dietary guidelines in T2D.

High Fat Diets Composed of Palm Stearin and Olive Oil Equally Exacerbate Liver Inflammatory Damage and Metabolic Stress in Mice

“…Lipids can act as proinflammatory molecules . In the current study, we evaluated the metabolic response of lipids and endotoxin treatments.…”

“…Lipids can act as proinflammatory molecules. [27] In the current study, we evaluated the metabolic response of lipids and endotoxin treatments. Both HFDs caused an increased level of fasting blood glucose (Figure 2A).…”

Modulation of Auditory Responses to Speech vs. Nonspeech Stimuli during Speech Movement Planning

“…Some authors have suggested that the phenomenon of auditory modulation may reflect general attentional processes rather than motor-to-auditory processes (see Jones et al, 2013 ; Horvath et al, 2015 ; Schröger et al, 2015a ). If so, it could be argued that our present paradigm’s use of a delayed-response task (i.e., participants actively withhold a planned utterance until the go signal is presented) reduces auditory attention in the speaking task.…”

“…Typically, these results have been interpreted in the context of theoretical frameworks of motor control involving efference copy and forward internal models (Waszak et al, 2012 ; Horvath et al, 2015 ; Schröger et al, 2015b ). Specifically, it has been suggested that the CNS uses an efference copy of issued motor commands and forward internal models to predict the auditory consequences of self-produced movements.…”

The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression

“…However, while the SUPP and PL were not isocaloric, it is unlikely that the negligible differences in the FAT and CHO content of SUPP contributed to the observed findings. A recent study by Horvath et al [ 27 ] demonstrated that postprandial plasma MCP-1 concentrations and monocyte CCR2 mRNA are unchanged following infusion of either glucose (20% dextrose solution: blood glucose increased to 220 mg·dL −1 over 30 min and sustained for 210 min), lipid (emulsion of 20% soy bean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and 76.55% water: infusion rate: 1.1 mL·kg·h −1 ) or combination treatment over the course of 4 h in healthy males [ 27 ]. Consequently, the differences between SUPP and PL in the present study appear to be related to the amino acid composition of SUPP.…”