Plasma amino acid levels are elevated in young, healthy low birth weight men exposed to short-term high-fat overfeeding

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

The Triglyceride Content in Skeletal Muscle Is Associated with Hepatic But Not Peripheral Insulin Resistance in Elderly Twins.

Context and Objective:Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins.Design and Participants:Seventy-four elderly same-sex twins underwent hyperinsulinemic euglycemic clamps preceded by an iv glucose tolerance test. Aerobic capacity (VO(2max)) and body composition (dual-energy x-ray absorptiometry scan) were determined in all twins. A biopsy from the vastus lateralis muscle was excised in the fasting state. The muscle triacylglycerol content was analyzed by biochemical extraction from these biopsies.Results:The percentage of total body fat was the only independent predictor of MT content. After adjustment for trunk fat percentages and sex, MT level was significantly associated to fasting plasma levels of glucose and insulin as well as hepatic insulin resistance. However, the association was weakened after adjustment for total fat percentages. A 1 sd (34.5 mmol/kg dry weight) increase in MT content was associated with a 24% increase of hepatic insulin resistance. No association between MT content and peripheral insulin sensitivity was observed.Conclusion:MT content is associated with hepatic but not peripheral insulin resistance in elderly twins. We speculate that MT content may reflect the general ectopic accumulation of triglycerides, including fat in the liver

Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men

We hypothesized that an increased, incomplete fatty acid beta‐oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5‐day high‐fat, high‐calorie diet. We demonstrated that LBW men had higher C2 and C4‐OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta‐oxidation relative to the tricarboxylic acid cycle flux. Also, they had higher C6‐DC, C10‐OH/C8‐DC, and total hydroxyl‐/dicarboxyl‐acylcarnitine levels, which may suggest an increased fatty acid omega‐oxidation in the liver. Furthermore, LBW and NBW men decreased several acylcarnitine levels in response to overfeeding, which is likely a result of an upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10‐OH/C8‐DC and total hydroxyl‐/dicarboxyl‐acylcarnitine levels tended to be negatively associated with the serum insulin level, and the total hydroxyl‐/dicarboxyl‐acylcarnitine level additionally tended to be negatively associated with the hepatic insulin resistance index. This indicates that an increased fatty acid omega‐oxidation could be a compensatory mechanism to prevent an accumulation of lipid species that impair insulin signaling

FRAX calculated without BMD resulting in a higher fracture risk than that calculated with BMD in women with early breast cancer

Background (and Purpose). The aim of this study was to investigate the importance of including the measurement of bone mineral density (BMD) in reliable fracture risk assessment for women diagnosed with early nonmetastatic breast cancer (EBC) before AI treatment if zoledronic acid is not an option. Material and Methods. One hundred and sixteen women with EBC were included in the study before initiating AI treatment. Most participants were osteopenic. The 10-year probability of hip fracture and major osteoporotic fracture was calculated with and without BMD based on clinical information collected at baseline using the fracture risk assessment (FRAX) tool. To compare data, the nonparametric tests were used. Results. There was a significant difference (p<0.001) in the number of high-risk and low-risk FRAX score of hip fracture between before and after including BMD values. The high-risk category decreased by 50.9%, while the low-risk category increased by 42.9%. In FRAX score of major osteoporotic the findings were similar (p<0.001): The high-risk and moderate-risk category decreased by 70.4% and 4.9%, respectively, while the low-risk category increased by 43.8% when including BMD value. When stratified by age, patients aged 65 years or older were at a significantly (p<0.001) higher risk of suffering a hip or major osteoporotic fracture, highlighting the importance of including BMD measurements in this age group. Conclusions. Our data support that DXA scanning of women with EBC should be performed to avoid overestimation of osteoporosis before AI treatment. It is particularly important in patients older than 65 years of age and when zoledronic acid is not an option

Plasma ceramide levels are altered in low and normal birth weight men in response to short-term high-fat overfeeding

AbstractLow birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. We hypothesised that LBW individuals exhibit an increased fatty acid flux into lipogenesis in non-adipose tissue with a resulting accumulation of lipotoxic lipids, including ceramides, in the blood. Therefore, we measured fasting plasma levels of 27 ceramides in 18 young, healthy, LBW men and 25 NBW controls after an isocaloric control diet and a 5-day high-fat, high-calorie diet by HPLC-HRMS. LBW men did not show elevated plasma ceramide levels after the control or high-fat, high-calorie diet. An increased fatty acid oxidation rate in these individuals during both diets may limit ceramide synthesis and thereby compensate for a likely increased fatty acid load to non-adipose tissue. Interestingly, LBW and NBW men decreased d18:0–18:1/d18:1–18:0 and d18:1–24:2/d18:2–24:1 levels and increased the d18:0–24:1a level in response to overfeeding. Plasma d18:0–24:1a and total ceramide levels were positively associated with the fasting blood glucose level and endogenous glucose production after the control diet, and the total ceramide level was in addition positively associated with hepatic insulin resistance. Further studies are needed to determine if lipotoxicity contributes to insulin resistance in LBW individuals.</jats:p