Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity and metabolic disease

2017 ◽  
Vol 18 ◽  
pp. 15-24 ◽  
Author(s):  
A. W. McHill ◽  
K. P. Wright
Keyword(s):  
Metabolic Disease ◽  
Energy Expenditure ◽  
Circadian Disruption ◽  
Human Obesity

scholarly journals The central melanocortin system and human obesity

2020 ◽  
Author(s):  
Yongjie Yang ◽  
Yong Xu
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Genetic Variants ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Human Obesity ◽  
Melanocortin System ◽  
Prevalence Of Obesity

Abstract The prevalence of obesity and the associated comorbidities highlight the importance of understanding the regulation of energy homeostasis. The central melanocortin system plays a critical role in controlling body weight balance. Melanocortin neurons sense and integrate the neuronal and hormonal signals, and then send regulatory projections, releasing anorexigenic or orexigenic melanocortin neuropeptides, to downstream neurons to regulate the food intake and energy expenditure. This review summarizes the latest progress in our understanding of the role of the melanocortin pathway in energy homeostasis. We also review the advances in the identification of human genetic variants that cause obesity via mechanisms that affect the central melanocortin system, which have provided rational targets for treatment of genetically susceptible patients.

scholarly journals Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 479
Author(s):  
Elizabeth L. Lieu ◽  
Neil Kelekar ◽  
Pratibha Bhalla ◽  
Jiyeon Kim
Keyword(s):  
Metabolic Disease ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Biochemical Properties ◽  
Biological Molecules ◽  
Diagnostic Tools ◽  
Inborn Errors ◽  
Mannose Metabolism

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

Chronic binge alcohol and ovariectomy dysregulate omental adipose tissue metaboproteome in simian immunodeficiency virus-infected female macaques

2021 ◽  
Author(s):  
Jonquil Marie Poret ◽  
Jessie J Guidry ◽  
Liz Simon ◽  
Patricia E. Molina
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Simian Immunodeficiency Virus ◽  
People Living With Hiv ◽  
Infected Female ◽  
Omental Adipose Tissue ◽  
Immunodeficiency Virus ◽  
Z Scores ◽  
Functional Pathways

Effective antiretroviral therapy (ART) has significantly reduced mortality of people living with HIV (PLWH), and the prevalence of at-risk alcohol use is higher among PLWH. Increased survival and aging of PLWH is associated with increased prevalence of metabolic comorbidities especially among menopausal women, and adipose tissue metabolic dysregulation may be a significant contributing factor. We examined the differential effects of chronic binge alcohol (CBA) administration and ovariectomy (OVX) on the omental adipose tissue (OmAT) proteome in a subset of simian immunodeficiency virus (SIV)-infected macaques of a longitudinal parent study. Quantitative discovery-based proteomics identified 1429 differentially expressed proteins. Ingenuity Pathway Analysis (IPA) was used to calculate z-scores, or activation predictions, for functional pathways and diseases. Results revealed protein changes associated with functional pathways centered around the "OmAT metaboproteome profile". Based on z-scores, CBA did not affect functional pathways of metabolic disease but dysregulated proteins involved in AMPK signaling and lipid metabolism. OVX-mediated proteome changes were predicted to promote pathways involved in glucose- and lipid-associated metabolic disease. Proteins involved in apoptosis, necrosis, and reactive oxygen species (ROS) pathways were also predicted to be activated by OVX, and these were predicted to be inhibited by CBA. These results provide evidence for the role of ovarian hormone loss in mediating OmAT metaboproteome dysregulation in SIV and suggest that CBA modifies OVX-associated changes. In the context of OVX, CBA administration produced larger metabolic and cellular effects, which we speculate may reflect a protective role of estrogen against CBA-mediated adipose tissue injury in female SIV-infected macaques.

scholarly journals Microvascular Endothelial Dysfunction in Human Obesity: Role of TNF-α

2018 ◽  
Vol 104 (2) ◽  
pp. 341-348 ◽  
Author(s):  
Agostino Virdis ◽  
Rocchina Colucci ◽  
Nunzia Bernardini ◽  
Corrado Blandizzi ◽  
Stefano Taddei ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Human Obesity ◽  
Tnf Α ◽  
Microvascular Endothelial

scholarly journals CRISPR-delivery particles targeting nuclear receptor–interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure

2018 ◽  
Vol 293 (44) ◽  
pp. 17291-17305 ◽  
Author(s):  
Yuefei Shen ◽  
Jessica L. Cohen ◽  
Sarah M. Nicoloro ◽  
Mark Kelly ◽  
Batuhan Yenilmez ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Energy Expenditure ◽  
Therapeutic Strategy ◽  
Gene Deletion ◽  
Cultured Cells ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Amphipathic Peptide ◽  
Cas9 Protein

RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune system CRISPR-Cas represent a powerful platform for gene deletion and editing. When used as a therapeutic approach, direct delivery of Cas9 protein and single-guide RNA (sgRNA) could circumvent the safety issues associated with plasmid delivery and therefore represents an attractive tool for precision genome engineering. Gene deletion or editing in adipose tissue to enhance its energy expenditure, fatty acid oxidation, and secretion of bioactive factors through a “browning” process presents a potential therapeutic strategy to alleviate metabolic disease. Here, we developed “CRISPR-delivery particles,” denoted CriPs, composed of nano-size complexes of Cas9 protein and sgRNA that are coated with an amphipathic peptide called Endo-Porter that mediates entry into cells. Efficient CRISPR-Cas9–mediated gene deletion of ectopically expressed GFP by CriPs was achieved in multiple cell types, including a macrophage cell line, primary macrophages, and primary pre-adipocytes. Significant GFP loss was also observed in peritoneal exudate cells with minimum systemic toxicity in GFP-expressing mice following intraperitoneal injection of CriPs containing Gfp-targeting sgRNA. Furthermore, disruption of a nuclear co-repressor of catabolism, the Nrip1 gene, in white adipocytes by CriPs enhanced adipocyte browning with a marked increase of uncoupling protein 1 (UCP1) expression. Of note, the CriP-mediated Nrip1 deletion did not produce detectable off-target effects. We conclude that CriPs offer an effective Cas9 and sgRNA delivery system for ablating targeted gene products in cultured cells and in vivo, providing a potential therapeutic strategy for metabolic disease.

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