Metabolomic Profiling of Fatty Acid and Amino Acid Metabolism in Youth With Obesity and Type 2 Diabetes

Mihalik, Stephanie J.; Michaliszyn, Sara F.; Heras, Javier de las; Bacha, Fida; Lee, So Jung; Chace, Donald H.; DeJesus, Victor; Vockley, Jerry; Arslanian, Silva

doi:10.2337/dc11-1577

Cited by 221 publications

(208 citation statements)

References 36 publications

(54 reference statements)

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“…Further, in a previous study we found that a lower serum histidine level in obese women, compared with non-obese healthy women, was associated with inflammation and oxidative stress [9]. Moreover, another recent study also found that the histidine level was lower in young obese individuals and in individuals with type 2 diabetes and was correlated with insulin sensitivity [10].…”

Section: Introductionmentioning

confidence: 83%

Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

et al. 2013

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Aims/hypothesis Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS). Methods A total of 100 obese women aged 33-51 years with BMI≥28 kg/m 2 and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n=50) or identical placebo (n=50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes. CI 0.60, 3.44] in histidine supplementation group (n=45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB. Conclusions/interpretation Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes. Trial registration www.chictr.org/cn/ChiCTR-TRC-11001551Electronic supplementary material The online version of this article

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Section: Introductionmentioning

confidence: 83%

Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

et al. 2013

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“…A family of aldo-keto reductase enzymes can use a wide variety of carbonyl compounds as their substrates and reduce these to their respective sugar alcohols (polyols) using NADPH ( Figure 2). Animal studies indicate an early increase in metabolic flow via all these pathways and suggest their potential damaging roles (35). Hyperglycemia also increases the non-enzymatic reaction of glucose and other glycating compounds derived both from glucose and from increased fatty acid oxidation, which generates advanced glycation end products in complication-prone cell types, including kidney cells (36).…”

Section: Figurementioning

confidence: 99%

Molecular mechanisms of diabetic kidney disease

Reidy¹,

et al. 2014

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Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide and the single strongest predictor of mortality in patients with diabetes. DKD is a prototypical disease of gene and environmental interactions. Tight glucose control significantly decreases DKD incidence, indicating that hyperglycemia-induced metabolic alterations, including changes in energy utilization and mitochondrial dysfunction, play critical roles in disease initiation. Blood pressure control, especially with medications that inhibit the angiotensin system, is the only effective way to slow disease progression. While DKD is considered a microvascular complication of diabetes, growing evidence indicates that podocyte loss and epithelial dysfunction play important roles. Inflammation, cell hypertrophy, and dedifferentiation by the activation of classic pathways of regeneration further contribute to disease progression. Concerted clinical and basic research efforts will be needed to understand DKD pathogenesis and to identify novel drug targets.

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“…Papers finally included n = 13 Zeng et al [19] Pietiläinen et al [41] Oberbach et al [9] Newgard et al [12] Karlsson et al [39] Wahl et al [11] Mihalik et al [21] Kim et al [14] McCormack et al [20] Okada et al [35] Warensjö et al [38] Moore et al [13] Study design …”

Section: Acylcarnitinesmentioning

confidence: 99%