Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis. Stark Romana,Reichenbach Alex,Andrews Zane B Molecular and cellular endocrinology The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin at POMC or NPY neurons may depend on appropriate nutrient-sensing in these neurons and we hypothesize carnitine metabolism is critical in the integrative processing. Future research is required to examine the neuron-specific effects of carnitine metabolism on concurrent nutrient- and hormonal-sensing in AgRP and POMC neurons. 10.1016/j.mce.2015.08.002

Effect of two fasting periods of different duration on ghrelin response to a mixed meal. Briatore Lucia,Andraghetti Gabriella,Cordera Renzo Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIM:The inhibitory effect of food on ghrelin secretion is reduced in several eating disorders such as restricting type anorexia nervosa, bulimia and obesity. These conditions are frequently characterised by irregular distribution of meals during the day. It is unknown whether two short fasting periods different duration affect ghrelin response to a mixed meal. Aim of the present study was to examine, in healthy volunteers, the effects of two fasting periods of different duration on pre- and post-prandial ghrelin concentrations after a standard mixed meal. METHODS AND RESULTS:Nine healthy men (mean age+/-S.E.M., 25.1+/-0.2 years; mean body mass index+/-S.E.M., 22.6+/-0.3kg/m2) were studied in 2 days after 12h of fasting (12F) and 17h of fasting (17F) with a within-subject repeated measure design. On both days they ate a standardized mixed meal. Before each meal hunger rating was evaluated with a visual analogue score. Blood samples for ghrelin, insulin, and glucose were collected at 0, 45, 60, 90, 120, 150 and 180min after meal. Comparing fasting values of 17F with 12F there was a significant increase in plasma ghrelin (160+/-20 vs. 146+/-18fmol/mL, P=0.015) and hunger rating (evaluated with a visual analogue scores) (7.0+/-0.3 vs. 5.1+/-0.4, P<0.003). A positive correlation between fasting ghrelin and hunger rating (r=0.52, P<0.01) was found. Circulating ghrelin decreased after both meals without any significant difference in relation with the previous length of fasting. Also postmeal ghrelin AUC as well as fasting and postmeal concentrations of insulin and glucose were similar after 12F and 17F. CONCLUSIONS:In healthy subjects a longer fasting period increases ghrelin concentration but did not affect post-prandial ghrelin response to a mixed meal. 10.1016/j.numecd.2005.07.004

L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study. Zhang Jun-jie,Wu Zhi-bing,Cai You-jin,Ke Bin,Huang Ying-juan,Qiu Chao-ping,Yang Yu-bing,Shi Lan-ying,Qin Jian Nutrition journal BACKGROUND:The present study aimed to determine that whether L-carnitine infusion could ameliorate fasting-induced adverse effects and improve outcomes. METHOD:In this 7-day, randomized, single-blind, placebo-controlled, pilot study, 15 metabolic syndrome (MetS) patients (11/4 F/M; age 46.9 ± 9.14 years; body mass index [BMI] 28.2 ± 1.8 kg/m2) were in the L-carnitine group (LC) and 15 (10/5 F/M; age 46.8 ± 10.9 years; BMI 27.1 ± 2.3 kg/m2) were in the control group (CT). All participants underwent a 5-day modified fasting therapy introduced with 2-day moderate calorie restriction. Patients in the LC group received 4 g/day of intravenous L-carnitine, while patients in the CT group were injected with saline. Blood pressure (BP), anthropometric characteristics, markers of liver function, metabolic indices (plasma glucose, lipid profiles, uric acid, free fatty acid and insulin) and hypersensitivity C-reactive protein were measured. Perceived hunger was recorded daily by self-rating visual analogue scales. Fatigue was evaluated by Wessely and Powell scores. RESULTS:In contrast to the CT group, total cholesterol, alanine aminotransferase, systolic and diastolic BP did not change significantly in the LC group after prolonged fasting. There were significant differences in weight loss (LC -4.6 ± 0.9 vs. CT -3.2 ± 1.1 kg, P = 0.03), and waist circumference (LC -5.0 ± 2.2 vs. CT -1.7 ± 1.16 cm, P < 0.001), waist hip ratio (LC -0.023 ± 0.017 vs. CT 0.012 ± 0.01, P < 0.001), insulin concentration (LC -9.9 ± 3.58 vs. CT -6.32 ± 3.44 µU/mL, P = 0.046), and γ-glutamyltransferase concentration (LC -7.07 ± 6.82 vs. CT -2.07 ± 4.18, P = 0.024). Perceived hunger scores were significantly increased (P < 0.05) in the CT group during starvation, which was alleviated with L-carnitine administration in the LC group. Physical fatigue (LC -3.2 ± 3.17 vs. CT 1.8 ± 2.04, P < 0.001) and fatigue severity (LC -11.6 ± 8.38 vs. CT 8.18 ± 7.32, P < 0.001) were significantly reduced in the LC group but were aggravated in the CT group. CONCLUSION:Intravenous L-carnitine can ameliorate fasting-induced hunger, fatigue, cholesterol abnormalities and hepatic metabolic changes and facilitate fasting-induced weight loss in MetS patients. TRIAL REGISTRATION:ChiCTR-TNRC-12002835. 10.1186/1475-2891-13-110

Influence of fasting during the night shift on next day eating behavior, hunger, and glucose and insulin levels: a randomized, three-condition, crossover trial. European journal of nutrition AIMS:To investigate the influence of fasting during the night shift on eating behavior, hunger, glucose and insulin levels the following day. METHODS:Study with 10 male police officers who have been working at night. Participants were tested under three different conditions separated by at least 6 days of washout in a randomized, crossover design: "Night Shift Fasting" (NSF)-two nights of fasting during the night shift; "Night Shift Eating" (NSE)-two nights with the consumption of a standardized meal during the night shift (678 ± 42 kcal consumed at ~ 0200 h); and "Nighttime Sleep" (NS)-two nights of sleep. The morning after, blood glucose and insulin and hunger ratings were assessed, and food intake was assessed with an ad libitum test meal. Food intake was also assessed throughout the remainder of the day using a food record. Generalized Estimating Equations were used to analyze the effect of experimental condition. RESULTS:Food intake during the test meal, especially of proteins and fats, was higher after fasting during the night shift compared to the other conditions (p < 0.05), whereas desire to eat scores were lower after the NSF compared to NSE condition (p = 0.043). Hunger levels were lower after the NSF compared to the NS condition (p = 0.012). Insulin and HOMA-IR were also lower in the morning after NSF (p < 0.001). CONCLUSION:Fasting during the night shift leads to not only a higher intake of energy and macronutrients both in the early morning after work and throughout the next day, but also lower insulin levels and HOMA-IR in the morning. REGISTRATION NUMBER OF CLINICAL TRIAL:NCT03800732. Initial release: 01/09/2019. Last release: 02/23/2022. 10.1007/s00394-022-03069-6

L-carnitine ameliorated weight loss in fasting therapy: A propensity score-matched study. Zhang Tingying,Zhang Li,Ke Bin,Sun Jiapan,Liu Taoli,Huang Yingjuan,Chen Xianhua,Liu Mengting,Li Fengxia,Luo Daohang,Qin Jian,Li Hui Complementary therapies in medicine l-carnitine infusion has been proven to reduce fasting-induced fatigue and hunger in patients with metabolic syndrome in our former study. However, the association between l-carnitine and clinical outcomes of fasting therapy is yet to be investigated. In this study, data from 192 patients who finished fasting therapy from September 2008 to July 2018 were reviewed, among which 142 patients received l-carnitine infusion in fasting regimen. Propensity matching was used to overcome retrospective bias. Patients' anthropometric measurements and metabolic markers were evaluated. After propensity matching, 40 patients were included in each group. Weight (-4.05 ± 1.65 kg vs -3.25 ± 1.68 kg, P = 0.031) and BMI (-1.51±0.61 kg/m vs -1.20 ± 0.62 kg/m, P = 0.036) decreased in both groups, but significantly more in l-carnitine group, while diastolic blood pressure (-1.67±9.82 mmHg vs -6.21±8.83 mmHg, P = 0.043) and triglycerides (-0.18±0.63 mmol/L vs -1.05±1.70 mmol/L, P = 0.007) decreased significantly more in non-l-carnitine group compared between groups, blood glucose did not differ significantly between groups. l-carnitine can boost the positive effects of fasting therapy on weight loss and maintain the stability of blood pressure. 10.1016/j.ctim.2019.03.020