Welcome To Dr. Schwarz' lab!
Most often, the disorders of carbohydrate (CHO) and fat metabolism have been studied
independently, and the importance of their mutual interaction has been overlooked.
My interest in the inter-relationship between CHO and fat metabolism was triggered
by the fact that, although individuals with insulin resistance and type 2 diabetes
are identified and treated for their problems with CHO homeostasis, they often have
equally important perturbations of fat homeostasis (dyslipidemia) and are more likely
to die from cardiovascular diseases. For these reasons, I have spent the past twelve
years concentrating my research efforts on whole body and hepatic fuel homeostasis
with special attention to the inter-relationship between carbohydrate and fat metabolism.
We felt that simultaneous study of the interplay between hepatic de novo lipogenesis (DNL), glucose production and gluconeogenesis (GNG) would lead to a better understanding of the pathophysiology at the origins of hypertriglyceridemia and hyperglycemia. Indeed, de novo lipogenesis (DNL), the pathway converting CHO to fat shares precursors with the GNG pathway and is a biochemical bridge between CHO and fat metabolism. This latter fact and our preliminary studies led me to hypothesize that hepatic DNL was an important regulatory pathway for diverting part of the GNG flux to better control GNG and glucose production.
We chose three main approaches to test this hypothesis in humans. One approach was to stimulate hepatic DNL by energy overfeeding with CHO or by feeding energy-balanced high CHO diets, and to monitor how this affected glucose production in healthy controls. The second approach was to utilize insulin resistant patients (such as obese and critically ill patients) who often have defects in glucose homeostasis and determine how these defects impacted DNL. The third approach was to test if inhibition of hepatic DNL had an impact on GNG and glucose production. The use of fructose as both a potent gluconeogenic and lipogenic precursor emphasized the importance of DNL in glucose homeostasis.
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