Tuesday, June 28, 2016

Other Publications in Peer-Reviewed Journals

After the publication of my honours project, I think this is a good time to summarise some other papers I’ve contributed to (as a general rule the first author made the most contribution and the last is the senior author).  These papers aren’t open access, but you can find them all at ResearchGate (links included).  You can also find them on PubMed by searching ‘hamley s’ (the perks of having an uncommon last name)

Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet [1]

Methods:

  • Half the mice were put on a high fat diet (HFD) and half on a standard low fat chow diet (LFD)
  • Some of mice were injected with a non-infectious virus to increase the expression of sphingosine kinase 1 

Results:

  • The HFD group developed obesity, impaired glucose tolerance, insulin resistance and fat accumulation in the liver
  • The HFD group had lower expression of sphingosine kinase 1 but not sphingosine kinase 2
  • Overexpression of sphingosine kinase 1 reduced liver triglycerides, de novo lipogenesis and lipogenic gene expression in the LFD group but not in the HFD group
  • Overexpression of sphingosine kinase 1 did not alter glucose tolerance or insulin sensitivity in mice on the LFD or HFD groups 

Implications: The idea of this study was that overexpression of sphingosine kinase 1 may reduce lipid accumulation in the liver, which would protect against the development the development of glucose intolerance and insulin resistance in the HFD group.  The first step on this process didn’t happen in the HFD group, which was unexpected.  So the fact that glucose intolerance and insulin resistance wasn’t altered in the overexpressing HFD group shouldn’t be surprising

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse [2]

Methods:

  • Half the mice were put on a HFD and half on a LFD
  • An OGTT was used with the glucose coming from a glucose isotope with all carbon atoms having an extra neutron (U-13C).  The use of U-13C glucose enables the metabolic fate of the ingested glucose to be tracked 

Results:

  • The HFD group developed obesity, impaired glucose tolerance and insulin resistance
  • The HFD group had less heavy carbon labelling in 3PGA (an intermediate of glycolysis), lactate, alanine and the TCA cycle, except for citrate 

Implications: The labelling data suggests that glucose metabolism in muscle is impaired with insulin resistance.  The labelling data also indicates that almost all the pyruvate enters the TCA via pyruvate dehydrogenase (PDH, cataplerosis) rather than pyruvate carboxylase (CK, anaplerosis)

In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic-hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach [3]

Methods:

  • Half the mice were put on a HFD and half on a LFD
  • An OGTT was used with the glucose coming from a glucose isotope with all carbon atoms having an extra neutron (U-13C)
  • The mice were infused with insulin and glucose to maintain elevated insulin levels and fasting glucose levels (hyperinsulinemic-euglycemic clamp) 

Results:

  • The HFD group developed obesity, impaired glucose tolerance and insulin resistance
  • Insulin resistance in the heart was present at 3 weeks after being on the HFD and does not get worse over time.  This is similar to muscle, but the liver develops insulin resistance earlier (present at 1 week)
  • There were no significant differences between the diets in heavy carbon labelling in the intermediates and products of glycolysis and TCA cycle, except for lower alanine in the HFD group 

Implications: The labelling data suggests that glucose metabolism in the heart isn’t reduced.  This is likely to be due to the higher glucose levels, which compensates for the insulin resistance.  Why this happens in heart but not muscle is unknown.  The labelling data also indicates that most of the pyruvate enters the TCA via PDH rather than PC anaplerosis.  The heart is a relatively small contributor to energy expenditure and whole body insulin sensitivity/glucose uptake, but this might be important for some heart diseases

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