Sleep disorders are frequently reported in autistic patients. Evidences suggest that increased oxidative stress and reduced antioxidants may play a major role in the pathogenesis of these disorders. Carnosine acts as an antioxidant, antitoxic and neuroprotective agent. The aim of this trial study was to examine the effects of carnosine supplementation on the sleep disorders and severity of autism core symptoms in autistic patients. In this double-blind, randomized clinical trial, 43 autistic patients (31 boys and 12 girls; aged 4 to 16 years) were divided into two groups of carnosine and control that received 500 mg of carnosine and 500 mg of placebo per day for 2 months, respectively. Sleep disorders were measured using Children's Sleep Habits Questionnaires. Gilliam Autism Rating Scale 2 was used to assess the effects of carnosine supplementation on the autism severity. Carnosine supplementation did not change anthropometric indices (p > 0.05) and showed no effect on autism severity (p > 0.05), whereas it significantly reduced sleep duration (p = 0.04), parasomnias (p = 0.02) and total sleep disorders score by 7.59% (p = 0.006) when compared with the control group. The results suggest that carnosine supplementation could be effective in improving sleep disturbances, in particular sleep duration and parasomnias subscales.

KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1/3 transcriptionally regulates Klf15 gene expression by directly binding to the liver-specific Klf15 promoter. To achieve this, we performed a precise in vivo promoter analysis combined with the genome-wide transcription-factor-screening method ''TFEL scan'', using our original Transcription Factor Expression Library (TFEL), which covers nearly all the transcription factors in the mouse genome. Hepatic Klf15 expression is significantly increased via FoxOs by attenuating insulin signaling. Furthermore, FoxOs elevate the expression levels of amino acid catabolic enzymes and suppress SREBP-1c via KLF15, resulting in accelerated amino acid breakdown and suppressed lipogenesis during fasting. Thus, the FoxO-KLF15 pathway contributes to switching the macronutrient flow in the liver under the control of insulin.

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