Fat, Inflammation and Insulin Resistance
Condition: Healthy Adults With Normal BMI
MeSH terms: Insulin Resistance; Inflammation
Study type: Interventional
Phase: Phase 4

Summary: 
      The combination of impaired insulin sensitivity and insulin secretion is thought to be the
      basis of type 2 diabetes. Increased free fatty acids levels impair insulin action in muscle
      and liver, but also systemic inflammation processes play a role in the development of insulin
      resistance.

      This study compares the effects of fat and inflammation on insulin sensitivity, systemic
      inflammation, energy metabolism, vascular system and neural function in healthy humans.
    

Detailed description: 
      A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) is known
      represent one key mechanism in the pathophysiology of insulin resistance, which is
      subsequently known to be the basis of the development of type 2 diabetes. But also
      inflammatory processes, also known as subclinical inflammation, have been shown to be
      independently associated with insulin resistance and diabetes development. The aim of this
      study is to analyse the causal relationship between FFA and inflammation in the induction of
      insulin resistance in healthy humans.

      It is known that the parenteral application of lipids over 4-6 hours results in an increase
      of FFA and a subsequent induction of a transient insulin resistance in peripheral tissues.
      Whether oral fat intake has similar effect is still unknown. On the other hand the oral
      intake of a high fat meal acutely increases intestinal permeability and thereby the levels of
      bacterial lipopolysaccharide (LPS) in the bloodstream. LPS is known to be a potent stimulator
      of immune response on a subclinical level accompanied by elevated levels of immune mediators,
      which in turn impair the insulin receptor signalling pathway leading to insulin resistance.
      Thus, in this study the effects of fat, both by an oral or parenteral fat load, and by a
      short-term LPS-infusion simulating the postprandial systemic LPS peak compared to a control
      infusion (glycerol) on insulin resistance is analysed. Insulin resistance and hepatic glucose
      production is determined by an hyperinsulinemic euglycemic clamp including glucose tracers.
      To detect the effects on the immune system on different levels, we measure 1) circulating
      levels of immune mediators by ELISA and bead-based mulitiplex assays, 2) gene expression of
      leukocytes, 3) subfractions of circulating leukocytes by FACS and 4) the stimulatory capacity
      of isolated lymphocytes and monocytes in vitro. Moreover, the effects of fat or inflammation
      on the function of the autonomic nervous system and the vasculature are studied. A second
      focus is the impact of the interventions on signal transduction and mitochondrial function in
      muscle and as well as on the metabolism and inflammation in subcutaneous adipose tissue in
      muscle and fat biopsies.
    

Intervention name(s): Fat/Inflammation effects
Intervention type(s): Biological
Intervention description(s): Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Healthy adults; Insulin sensitivity