Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates

Mouse studies linking adropin, a peptide hormone encoded by the energy homeostasis–associated (ENHO) gene, to biological clocks and to glucose and lipid metabolism suggest a potential therapeutic target for managing diseases of metabolism. However, adropin's roles in human metabolism are unclear. In silico expression profiling in a nonhuman primate diurnal transcriptome atlas (GSE98965) revealed a dynamic and diurnal pattern of ENHO expression. ENHO expression is abundant in brain, including ventromedial and lateral hypothalamic nuclei regulating appetite and autonomic function. Lower ENHO expression is present in liver, lung, kidney, ileum, and some endocrine glands. Hepatic ENHO expression associates with genes involved in glucose and lipid metabolism. Unsupervised hierarchical clustering identified 426 genes co-regulated with ENHO in liver, ileum, kidney medulla, and lung. Gene Ontology analysis of this cluster revealed enrichment for epigenetic silencing by histone H3K27 trimethylation and biological processes related to neural function. Dietary intervention experiments with 59 adult male rhesus macaques indicated low plasma adropin concentrations were positively correlated with fasting glucose, plasma leptin, and apolipoprotein C3 (APOC3) concentrations. During consumption of a high-sugar (fructose) diet, which induced 10% weight gain, animals with low adropin had larger increases of plasma leptin and more severe hyperglycemia. Declining adropin concentrations were correlated with increases of plasma APOC3 and triglycerides. In summary, peripheral ENHO expression associates with pathways related to epigenetic and neural functions, and carbohydrate and lipid metabolism, suggesting co-regulation in nonhuman primates. Low circulating adropin predicts increased weight gain and metabolic dysregulation during consumption of a high-sugar diet.

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Plasma Leptin, Ghrelin and Indexes of Glucose and Lipid Metabolism in Relation to the Appearance of Post-Weaning Oestrus in Mediterranean Obese Sows (Iberian Pig)

Reproduction in Domestic Animals ◽

10.1111/j.1439-0531.2010.01680.x ◽

2011 ◽

Vol 46 (3) ◽

pp. 558-560 ◽

Cited By ~ 8

Author(s):

L Torres-Rovira ◽

P Pallares ◽

E Vigo ◽

P Gonzalez-Añover ◽

R Sanchez-Sanchez ◽

...

Keyword(s):

Lipid Metabolism ◽

Glucose And Lipid Metabolism ◽

Iberian Pig ◽

Plasma Leptin

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COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00822-x ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Xi He ◽

Chenshu Liu ◽

Jiangyun Peng ◽

Zilun Li ◽

Fang Li ◽

...

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Isobutyric Acid ◽

Transcriptional Level ◽

Metabolic Factors ◽

Metabolic Complications ◽

Glucose And Lipid Metabolism ◽

Metabolic Dysregulation ◽

Underlying Mechanisms ◽

New Onset

AbstractAbnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

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Establishment of Mouse Models of Psoriasis with Blood Stasis Syndrome Complicated with Glucose and Lipid Metabolism Disorders

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6419509 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Ying Luo ◽

Yi Ru ◽

Huaibo Zhao ◽

Liu Liu ◽

Seokgyeong Hong ◽

...

Keyword(s):

Lipid Metabolism ◽

Chinese Medicine ◽

Mouse Models ◽

Metabolic Disorders ◽

Blood Stasis ◽

Blood Stasis Syndrome ◽

Control Group ◽

High Sugar ◽

Glucose And Lipid Metabolism ◽

Lipid Metabolism Disorders

Background. Psoriasis has been reported as a high-risk factor for quality of life and survival rate in patients with metabolic disorder. However, there is no animal model for studying this disease. This study aimed to establish and evaluate mouse models of psoriasis with blood stasis syndrome (which is a key to psoriasis pathogenesis, according to Chinese Medicine) complicated with metabolic disorders. Method. Forty-five C57BL/6 mice were randomly divided into the blank control (Control), psoriasis (Imiquimod (IMQ)), psoriasis with metabolic disorders (IMQ + streptozotocin (STZ)), psoriasis with blood stasis syndrome (BSS) (IMQ + BSS), and psoriasis with blood stasis syndrome complicated with metabolic disorders (IMQ + STZ + BSS) groups (n = 9 mice/group). Psoriasis lesions were induced using IMQ cream (on both the ears and back, except in the Control group). Mice of the IMQ + BSS group were fed a half-fat, high-sugar diet and stimulated with ice-water swimming every day. Mice of the IMQ + STZ group were fed a half-fat, high-sugar diet and injected with STZ. Mice of the IMQ + STZ + BSS group were subjected to the same treatments as the IMQ + STZ and IMQ + BSS groups. After induction, the mice in each group were observed for vital signs, ear thickness, body weight, and psoriasis area and severity index (PASI) score. The mice were fasted for 12 h before determination of related laboratory serum indexes. Dorsal skin lesions, aortic arch pathology sections, and signal transducer and activator of transcription 3 (STAT3) were examined by H&E staining and immunohistochemistry. Results. Laboratory indexes in the four model groups were significantly different from those in the Control group (p<0.01); indicators of the IMQ + STZ, IMQ + BSS, and IMQ + STZ + BSS groups showed varying degrees of difference from those of the IMQ group. Conclusions. The established mouse models of psoriasis blood stasis syndrome complicated with glucose and lipid metabolism disorders met the clinical and Chinese Medicine characteristics, and thus they could be used as animal models in future studies of psoriasis complicated with glucose and lipid metabolism disorders.

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GLP1 receptor agonism protects against acute olanzapine-induced hyperglycemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00309.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. E1101-E1111 ◽

Cited By ~ 1

Author(s):

Kyle D. Medak ◽

Hesham Shamshoum ◽

Willem T. Peppler ◽

David C. Wright

Keyword(s):

Lipid Metabolism ◽

Side Effects ◽

Antipsychotic Drug ◽

Antipsychotic Drugs ◽

Glucose And Lipid Metabolism ◽

Metabolic Dysregulation ◽

Metabolic Side Effects ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Effective Adjunct

Antipsychotic drugs cause rapid perturbations in glucose and lipid metabolism. In the present study we have demonstrated that cotreatment with glucagon-like peptide 1 (GLP1) receptor agonists, such as liraglutide, protects against metabolic dysregulation caused by the antipsychotic drug olanzapine. These findings suggest that pharmacological targeting of the GLP1 receptor could be an effective adjunct approach to mitigate the harmful acute metabolic side effects of antipsychotic drugs.

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Clinical Considerations in Selecting and Using Atypical Antipsychotics

CNS Spectrums ◽

10.1017/s1092852900025177 ◽

2005 ◽

Vol 10 (S10) ◽

pp. 12-19 ◽

Cited By ~ 5

Author(s):

John W. Newcomer

Keyword(s):

Lipid Metabolism ◽

Weight Gain ◽

Atypical Antipsychotics ◽

Risks And Benefits ◽

Glucose And Lipid Metabolism ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Lower Weight Gain ◽

Clinical Considerations ◽

Improve Health

AbstractPatients with schizophrenia have a 20% shorter lifespan than people without the disorder. An increased risk of cardiovascular morbidity and mortality is also associated with schizophrenia. Atypical antipsychotics may contribute to the prevalence of cardiovascular disease by causing weight gain and increased adiposity, risk of insulin resistance, hyperglycemia, diabetes, and hyperlipidemia. Atypical antipsychotics that produce the greatest degree of weight gain also appear to impose the greatest risk of diabetes and hyperlipidemia. Recent evidence suggests that atypical antipsychotics may even affect glucose and lipid metabolism independent of weight gain. Among the currently marketed antipsychotics, clozapine and olanzapine appear to produce the greatest degree of weight gain. Moderate increases in weight are also observed with quetiapine and risperidone. Only ziprasidone and aripiprazole appear to be weight neutral. Atypical antipsychotics that produce the greatest degree of weight gain also appear to carry the greatest risk of diabetes and hyperlipidemia. Because of the potential for atypical antipsychotics to cause weight gain and adversely affect glucose and lipid metabolism, clinical monitoring of these parameters is critical. Dietary modification and exercise may be critical to addressing antipsychotic-induced weight gain and its consequences. In patients with persistent weight gain, evaluation of the risks and benefits of ongoing medications and consideration of switching to an antipsychotic with lower weight-gain liability may improve health outcomes.

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Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy

Translational Psychiatry ◽

10.1038/s41398-021-01778-w ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Chuanjun Zhuo ◽

Yong Xu ◽

Weihong Hou ◽

Jiayue Chen ◽

Qianchen Li ◽

...

Keyword(s):

Lipid Metabolism ◽

Weight Gain ◽

Side Effects ◽

Antipsychotic Drugs ◽

Mammalian Target Of Rapamycin ◽

Mtor Pathway ◽

Target Of Rapamycin ◽

Glucose And Lipid Metabolism ◽

Pathway Activation ◽

Extrapyramidal Motor

AbstractAntipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.

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Disturbed gut microbiota and bile homeostasis in Giardia-infected mice contributes to metabolic dysregulation and growth impairment

Science Translational Medicine ◽

10.1126/scitranslmed.aay7019 ◽

2020 ◽

Vol 12 (565) ◽

pp. eaay7019

Author(s):

Ambre Riba ◽

Kasra Hassani ◽

Alesia Walker ◽

Niels van Best ◽

Dunja von Zeschwitz ◽

...

Keyword(s):

Lipid Metabolism ◽

Weight Gain ◽

Bile Acid ◽

Body Weight Gain ◽

Protozoan Parasite ◽

Bile Secretion ◽

Neonatal Mouse ◽

Bile Acid Metabolism ◽

Metabolic Dysregulation ◽

Endemic Areas

Although infection with the human enteropathogen Giardia lamblia causes self-limited diarrhea in adults, infant populations in endemic areas experience persistent pathogen carriage in the absence of diarrhea. The persistence of this protozoan parasite in infants has been associated with reduced weight gain and linear growth (height-for-age). The mechanisms that support persistent infection and determine the different disease outcomes in the infant host are incompletely understood. Using a neonatal mouse model of persistent G. lamblia infection, we demonstrate that G. lamblia induced bile secretion and used the bile constituent phosphatidylcholine as a substrate for parasite growth. In addition, we show that G. lamblia infection altered the enteric microbiota composition, leading to enhanced bile acid deconjugation and increased expression of fibroblast growth factor 15. This resulted in elevated energy expenditure and dysregulated lipid metabolism with reduced adipose tissue, body weight gain, and growth in the infected mice. Our results indicate that this enteropathogen’s modulation of bile acid metabolism and lipid metabolism in the neonatal mouse host led to an altered body composition, suggesting how G. lamblia infection could contribute to growth restriction in infants in endemic areas.

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