Abstract
Low birth weight (LBW) individuals exhibit a disproportionately increased, incomplete fatty acid oxidation and a decreased glucose oxidation, compared with normal birth weight (NBW) individuals, and furthermore have an increased risk of developing insulin resistance and type 2 diabetes. We hypothesized that changes in amino acid metabolism may occur parallel to alterations in fatty acid and glucose oxidation, and could contribute to insulin resistance. Therefore, we measured fasting plasma levels of 15 individual or pools of amino acids in 18 LBW and 25 NBW men after an isocaloric control diet and after a 5‐day high‐fat, high‐calorie diet. We demonstrated that LBW and NBW men increased plasma alanine levels and decreased valine and leucine/isoleucine levels in response to overfeeding. Also, LBW men had higher alanine, proline, methionine, citrulline, and total amino acid levels after overfeeding compared with NBW men. Alanine and total amino acid levels tended to be negatively associated with the insulin‐stimulated glucose uptake after overfeeding. Therefore, the higher amino acid levels in LBW men could be a consequence of their reduction in skeletal muscle insulin sensitivity due to overfeeding with a possible increased skeletal muscle proteolysis and/or could potentially contribute to an impaired insulin sensitivity. Furthermore, the alanine level was negatively associated with the plasma acetylcarnitine level and positively associated with the hepatic glucose production after overfeeding. Thus, the higher alanine level in LBW men could be accompanied by an increased anaplerotic formation of oxaloacetate and thereby an enhanced tricarboxylic acid cycle activity and as well an increased gluconeogenesis.
Highlights
Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes later in life, compared with normal birth weight (NBW) individuals, when exposed to an affluent life style such as overfeeding (Hales et al 1991; Barker et al 1993; Hofman et al 2004; Vaag et al 2006)
We demonstrated that LBW and NBW men increased plasma alanine levels and decreased valine and leucine/isoleucine levels in response to overfeeding
We have found that LBW men exhibit an increased fatty acid oxidation along with a decreased glucose oxidation at night as determined during an isocaloric control diet and a high-fat, high-calorie diet compared with NBW men (Brons et al 2013, 2015)
Summary
Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes later in life, compared with normal birth weight (NBW) individuals, when exposed to an affluent life style such as overfeeding (Hales et al 1991; Barker et al 1993; Hofman et al 2004; Vaag et al 2006). In the present extension study, we hypothesized that the changes in fatty acid and glucose oxidation partitioning in LBW individuals would be associated with changes in plasma amino acid levels, reflecting the need for an adequate supply of TCA cycle intermediates to allow an efficient acetyl-CoA oxidation in the TCA cycle (Fig. 1) Such changes could be parts of the adverse metabolic events leading to insulin resistance in LBW individuals. In order to test our hypotheses, we measured fasting plasma levels of 15 individual or pools of amino acids in LBW and NBW men after an isocaloric control diet and after a 5-day high-fat, high-calorie diet, and associated these levels to the plasma acetylcarnitine level, as a measure of the intracellular acetyl-CoA level, and to measures of hepatic and peripheral insulin sensitivity
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