Neonatal overfeeding during lactation rapidly and permanently misaligns the hepatic circadian rhythm and programmes adult NAFLD

Ribas-Aulinas, Francesc; Ribó, Sílvia; Parra-Vargas, Marcela; Fernández-Pérez, Antonio; Cebrià, Judith; Guardiola-Perello, Maria; Ramón-Krauel, Marta; Lerín, Carles; Díaz, Rubén; Kalko, Susana G.; Vallejo, Mario; Dı́ez-Noguera, Antoni; Cambras, Trinitat; Jiménez-Chillarón, Josep C.

doi:10.1016/j.molmet.2021.101162

Cited by 13 publications

(11 citation statements)

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“…Some evidence supports that the TRFs improve metabolic health, at least in part, through modulating the circadian rhythm [ 29 , 30 ]. Indeed, we had previously shown that hepatic steatosis in SL mice might be attributed to dysregulation of peripheral clock genes [ 15 ]. Hence, here we speculate that normalization of TAG concentration in our model might be accomplished through re-setting the hepatic circadian rhythm.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in our model the TRFs primarily modified those clock genes that are partially entrained by nutritional cues, including Per1-3 or Cry1-2 [ 20 , 32 , 33 ]. In turn, Period and Cryptochrome genes can regulate hepatic lipid content through directly influencing the expression of lipogenic genes [ 15 , 26 ]. Hence, here we proposed that the TRFs contribute to restore hepatic lipid content, in part, through re-setting the clock genes, which in turn, modify the expression of lipid-related genes.…”

Section: Discussionmentioning

confidence: 99%

“…The liver played a major role in triggering early-onset insulin resistance. At the molecular level, hepatic steatosis and hepatic insulin resistance were attributed, in part, to misalignment of the hepatic circadian rhythm [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity

et al. 2021

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Background: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. Methods: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two independent short-term chrono-nutritional interventions might improve metabolic health in 1-month-old pre-pubertal SL mice. Both TRFs comprised 8 h feeding/14 h fasting. In the first one (TRF1) Control and SL mice had access to the diet for 8 h during the dark phase. In the second intervention (TRF2) food was available during the light:dark transitions. Results: TRF1 did not alter food intake nor ameliorate adiposity in SL-TRF1. In contrast, SL-TRF2 mice showed unintentional reduction of caloric intake, which was accompanied by reduced total body weight and adiposity. Strikingly, hepatic triglyceride content was completely normalized in SL-TRF1 and SL-TRF2 mice, when compared to the ad lib-fed SL mice. These effects were partially mediated by (i) clock-dependent signals, which might modulate the expression of Pparg or Cpt1a, and (ii) clock-independent signals, such as fasting itself, which could influence Fasn expression. Conclusions: Time-restricted feeding is an effective and feasible nutritional intervention to improve metabolic health, namely hepatic steatosis, in a model of childhood obesity. These data open new avenues for future safe and efficient chrono-nutritional interventions aimed to improve metabolic health in children with overweight/obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity

et al. 2021

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“…Energy expenditure (EE) was calculated as EE = (3.185 + 1.232 × RER) × . Total locomotor activity was simultaneously measured using an infrared photocell beam interruption method, carried out using the TSE Phenomaster, as described previously [ 13 ]. Analysis was performed using the TSE Phenomaster Mouse software V5.1.7 (TSE Systems).…”

Section: Methodsmentioning

confidence: 99%

The second-generation antipsychotic drug aripiprazole modulates the serotonergic system in pancreatic islets and induces beta cell dysfunction in female mice

et al. 2021

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Aims/hypothesis Second-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet function and plasticity. Methods We analysed the functional adaptation of beta cells in 12-week-old B6;129 female mice fed an olanzapine- or aripiprazole-supplemented diet (5.5–6.0 mg kg−1 day−1) for 6 months. Glucose and insulin tolerance tests, in vivo glucose-stimulated insulin secretion and indirect calorimetry were performed at the end of the study. The effects of SGAs on beta cell plasticity and islet serotonin levels were assessed by transcriptomic analysis and immunofluorescence. Insulin secretion was assessed by static incubations and Ca2+ fluxes by imaging techniques. Results Treatment of female mice with olanzapine or aripiprazole for 6 months induced weight gain (p<0.01 and p<0.05, respectively), glucose intolerance (p<0.01) and impaired insulin secretion (p<0.05) vs mice fed a control chow diet. Aripiprazole, but not olanzapine, induced serotonin production in beta cells vs controls, likely by increasing tryptophan hydroxylase 1 (TPH1) expression, and inhibited Ca2+ flux. Of note, aripiprazole increased beta cell size (p<0.05) and mass (p<0.01) vs mice fed a control chow diet, along with activation of mechanistic target of rapamycin complex 1 (mTORC1)/S6 signalling, without preventing beta cell dysfunction. Conclusions/interpretation Both SGAs induced weight gain and beta cell dysfunction, leading to glucose intolerance; however, aripiprazole had a more potent effect in terms of metabolic alterations, which was likely a result of its ability to modulate the serotonergic system. The deleterious metabolic effects of SGAs on islet function should be considered while treating patients as these drugs may increase the risk for development of the metabolic syndrome and diabetes. Graphical abstract

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“…This study showed that there was no statistically significant positive correlation between non-fasting total cholesterol (TC), non-fasting non-HDL-C and non-fasting (LDL and weight. According to the results of one study, obesity was more closely associated with negative changes in children's lipid profiles than simply being overweight (17) .…”

Section: Discussionmentioning

confidence: 99%

Screening of Dyslipidemia and Obesity among Children in Zagazig University Hospitals

Ali¹,

El-Salam²,

Arafa³

et al. 2021

The Egyptian Journal of Hospital Medicine

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Background: Westerners are well aware of plasma lipid problems, which are becoming increasingly important in the Middle East. The European Expert Panel has advocated universal screening as a preferable approach of hypercholesterolemia screening as a part of the primary preventive effort. Objective: To assess the relation between dyslipidemia and its risk factors; age and body mass index. Patients and Methods: A cross-sectional study that included 357 of children who visited the Pediatrics General Outpatient Clinic at Zagazig University Hospitals. All subjects were subjected to full history taking, general examination, anthropometric measurements, blood pressure, and laboratory investigations including: non-fasting and fasting lipid profiles. Results: Non-fasting total cholesterol (TC) of ≥ 200 was (14.3%) and < 200 was (85.7%). Non-fasting (LDL) of ≥ 130 was (16.8%) and <130 was (83.2%). HDL category of < 40 was (61.3%) and ≥ 40 was (38.7%). There was no statistically significant difference between age, sex and lipid profiles. There was statistically significant positive correlation between non-fasting triglycerides (TG) and non-fasting HDL and non-fasting non-HDL-C. Conclusion: Obesity was associated with the prevalence of at least one abnormal lipid level. This highlights the importance of paying greater attention to the prevention of cardiovascular disease and obesity in children from an early age.

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Neonatal overfeeding during lactation rapidly and permanently misaligns the hepatic circadian rhythm and programmes adult NAFLD

Cited by 13 publications

References 74 publications

Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity

Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity

The second-generation antipsychotic drug aripiprazole modulates the serotonergic system in pancreatic islets and induces beta cell dysfunction in female mice

Screening of Dyslipidemia and Obesity among Children in Zagazig University Hospitals

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