scholarly journals Female Mice with Selenocysteine tRNA Deletion in Agrp Neurons Maintain Leptin Sensitivity and Resist Weight Gain While on a High-Fat Diet

2021 ◽  
Vol 22 (20) ◽  
pp. 11010
Author(s):  
Daniel J. Torres ◽  
Matthew W. Pitts ◽  
Lucia A. Seale ◽  
Ann C. Hashimoto ◽  
Katlyn J. An ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Redox Balance ◽  
Conditional Knockout ◽  
Sexually Dimorphic ◽  
High Fat ◽  
Leptin Sensitivity ◽  
To Come ◽  
Insight Into

The role of the essential trace element selenium in hypothalamic physiology has begun to come to light over recent years. Selenium is used to synthesize a family of proteins participating in redox reactions called selenoproteins, which contain a selenocysteine residue in place of a cysteine. Past studies have shown that disrupted selenoprotein expression in the hypothalamus can adversely impact energy homeostasis. There is also evidence that selenium supports leptin signaling in the hypothalamus by maintaining proper redox balance. In this study, we generated mice with conditional knockout of the selenocysteine tRNA[Ser]Sec gene (Trsp) in an orexigenic cell population called agouti-related peptide (Agrp)-positive neurons. We found that female TrspAgrpKO mice gain less weight while on a high-fat diet, which occurs due to changes in adipose tissue activity. Female TrspAgrpKO mice also retained hypothalamic sensitivity to leptin administration. Male mice were unaffected, however, highlighting the sexually dimorphic influence of selenium on neurobiology and energy homeostasis. These findings provide novel insight into the role of selenoproteins within a small yet heavily influential population of hypothalamic neurons.

Beneficial effects of tamoxifen on leptin sensitivity in young mice fed a high fat diet: Role of estrogen receptor α and cytokines

Life Sciences ◽  
2020 ◽  
Vol 246 ◽  
pp. 117384
Author(s):  
Zeinab Farhadi ◽  
Mohammad Khaksari ◽  
Hossein Azizian ◽  
Abbas Mortazaeizadeh ◽  
Mohammad Shabani ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
High Fat Diet ◽  
Estrogen Receptor Α ◽  
High Fat ◽  
Beneficial Effects ◽  
Leptin Sensitivity ◽  
Young Mice

scholarly journals Selenium Regulates Hypothalamic Control of Energy Metabolism in a Sexually Dimorphic Manner

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1844-1844
Author(s):  
Daniel Torres ◽  
Matthew Pitts ◽  
Lucia Seale ◽  
Ann Hashimoto ◽  
Katlyn An ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Metabolic Phenotype ◽  
Sexually Dimorphic ◽  
High Fat ◽  
Diet Induced Obesity

Abstract Objectives The trace element selenium (Se) is known mainly for its antioxidant properties and is critical for proper brain function. The role of Se in regulating energy metabolism, and the sexually dimorphic nature of Se functions, however, are underappreciated, and warrant increased attention. Recent work in our lab has highlighted the importance of Se utilization in hypothalamic regulation of energy metabolism. Dietary Se is incorporated into selenoproteins in the form of the unique amino acid selenocysteine (Sec). The objective of this study was to assess the role of selenoproteins in Agouti-related peptide (Agrp)-positive neurons, an orexigenic sub-population of the hypothalamus. Methods We generated mice with Agrp-Cre-driven deletion of selenocysteine tRNA (Trsp-Agrp KO mice), which is essential for Sec incorporation into selenoproteins, thus ablating selenoprotein synthesis in Agrp-positive neurons. The metabolic phenotype of Trsp-Agrp KO mice challenged with a high-fat diet was characterized via glucose tolerance test (i.p. injection) and the use of analytical chambers to measure food intake and respiratory metabolism. Prior to sacrifice, mice were challenged with leptin (i.p. injection) to assess neuronal leptin responsivity via immunohistochemistry and western blot. Brown adipose tissue (BAT) morphology and thermogenic protein expression were also analyzed. Results Female Trsp-Agrp KO mice displayed resistance to diet-induced obesity, which was accompanied by improved glucose tolerance and elevated energy expenditure levels without changes in food intake. Female Trsp-Agrp KO mice also had greater leptin sensitivity and showed signs of elevated BAT thermogenesis. Male Trsp-Agrp KO mice displayed no changes in metabolic phenotype. Conclusions Loss of selenoproteins in Agrp-positive neurons of the hypothalamus promotes energy expenditure and reduces diet-induced obesity in a sexually dimorphic manner, leading to resistance to a high-fat diet in females. Funding Sources This work was funded by grant support from the National Institute of Diabetes and Digestive and Kidney Diseases (MJB) and Ola HAWAII, a grant from the National Institute on Minority Health and Health Disparities.

scholarly journals Role of the saturated fatty acid palmitate in the interconnected hypothalamic control of energy homeostasis and biological rhythms

2018 ◽  
Vol 315 (2) ◽  
pp. E133-E140 ◽  
Author(s):  
Erika K. Tse ◽  
Ashkan Salehi ◽  
Matthew N. Clemenzi ◽  
Denise D. Belsham
Keyword(s):  
Circadian Rhythms ◽  
Cell Lines ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Clock Gene ◽  
Neuronal Cell ◽  
Whole Body ◽  
High Fat ◽  
Neuronal Cell Lines

The brain, specifically the hypothalamus, controls whole body energy and glucose homeostasis through neurons that synthesize specific neuropeptides, whereas hypothalamic dysfunction is linked directly to insulin resistance, obesity, and type 2 diabetes mellitus. Nutrient excess, through overconsumption of a Western or high-fat diet, exposes the hypothalamus to high levels of free fatty acids, which induces neuroinflammation, endoplasmic reticulum stress, and dysregulation of neuropeptide synthesis. Furthermore, exposure to a high-fat diet also disrupts normal circadian rhythms, and conversely, clock gene knockout models have symptoms of metabolic disorders. While whole brain/animal studies have provided phenotypic end points and important clues to the genes involved, there are still major gaps in our understanding of the intracellular pathways and neuron-specific components that ultimately control circadian rhythms and energy homeostasis. Because of its complexity and heterogeneous nature, containing a diverse mix cell types, it is difficult to dissect the critical hypothalamic components involved in these processes. Of significance, we have the capacity to study these individual components using an extensive collection of both embryonic- and adult-derived, immortalized hypothalamic neuronal cell lines from rodents. These defined neuronal cell lines have been used to examine the impact of nutrient excess, such as palmitate, on circadian rhythms and neuroendocrine signaling pathways, as well as changes in vital neuropeptides, leading to the development of neuronal inflammation; the role of proinflammatory molecules in this process; and ultimately, restoration of normal signaling, clock gene expression, and neuropeptide synthesis in disrupted states by beneficial anti-inflammatory compounds in defined hypothalamic neurons.

scholarly journals Role of astroglia in diet-induced central neuroplasticity

2019 ◽  
Vol 121 (4) ◽  
pp. 1195-1206 ◽  
Author(s):  
Courtney Clyburn ◽  
Kirsteen N. Browning
Keyword(s):  
Systemic Inflammation ◽  
High Fat Diet ◽  
Type Ii Diabetes ◽  
Energy Homeostasis ◽  
High Fat ◽  
Health Crisis ◽  
Diet Induced Obesity ◽  
Reward Pathways ◽  
Astroglial Activation

Obesity, characterized by increased adiposity that develops when energy intake outweighs expenditure, is rapidly becoming a serious health crisis that affects millions of people worldwide and is associated with severe comorbid disorders including hypertension, cardiovascular disease, and type II diabetes. Obesity is also associated with the dysregulation of central neurocircuits involved in the control of autonomic, metabolic, and cognitive functions. Systemic inflammation associated with diet-induced obesity (DIO) has been proposed to be responsible for the development of these comorbidities as well as the dysregulation of central neurocircuits. A growing body of evidence suggests, however, that exposure to a high-fat diet (HFD) may cause neuroinflammation and astroglial activation even before systemic inflammation develops, which may be sufficient to cause dysregulation of central neurocircuits involved in energy homeostasis before the development of obesity. The purpose of this review is to summarize the current literature exploring astroglial-dependent modulation of central circuits following exposure to HFD and DIO, including not only dysregulation of neurocircuits involved in energy homeostasis and feeding behavior, but also the dysregulation of learning, memory, mood, and reward pathways.

scholarly journals OR12-06 Nuclear Receptor CAR Protects Female Mice from the Development of Diet-Induced Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fabiana Layla Oliviero ◽  
Céline Lukowicz ◽  
Lucile Mary ◽  
Laila Lakhal
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
Nuclear Receptor ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Sexually Dimorphic ◽  
High Fat ◽  
Knock Out ◽  
Female Mice

Abstract NAFLD (Non Alcoholic Fatty Liver Disease) has become the most common cause of chronic liver disease in many developed countries worldwide and represents a major health concern. The prevalence of NAFLD is sexually dimorphic with men suspected to be more susceptible to the development of hepatic steatosis than women. Women are mostly protected until hormonal imbalance induced by menopause. Nuclear receptor CAR (Constitutive Androstan Receptor) is at the crossroads between endocrine and metabolic regulations and could therefore represent an interesting therapeutic target. It is primarily expressed in the liver and involved in the catabolism of hormones such as thyroid hormones, corticosteroids and estrogens. In addition, several studies reveal a metabolic role of CAR through regulation of major hepatic pathways such as neoglucogenesis, beta-oxidation and de novo lipogenesis. Our research is aimed at better understanding the role of CAR using a mouse model genetically deficient for CAR. To explore the metabolic functions of CAR, knock-out male and female mice were subjected to a high fat diet (HFD) for 16 weeks. Concomitant CAR deletion and high fat diet induces sexually dimorphic metabolic disorders. Knock-out of CAR in males exacerbates HFD-induced fasted hyperglycemia whereas in females, it aggravates body weight gain and adipose tissue accumulation. In accordance with epidemiological studies revealing a protection of women from the development of hepatic steatosis, HFD-fed WT female mice present less important hepatic steatosis than HFD-fed WT male mice. However, following CAR deletion, HFD-fed female mice develop a severe steatosis along with important hepatic injury. Ongoing studies aim to understand the transcriptomic and endocrine dysregulations that may explain these phenotypes. These results reveal a previously unrecognized dimorphic role of CAR in energy homeostasis and highlights its involvement in the protection of female mice towards the development of hepatic steatosis. Overall, this research provides further insights in the pathogenesis of NAFLD and its dimorphic prevalence.

The role of rice bran extract on acetyl CoA carboxylase in liver of rats fed a high-fat diet

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
C Charkhonpunya ◽  
S Sireeratawong ◽  
S Komindr ◽  
N Lerdvuthisopon
Keyword(s):  
Rice Bran ◽  
High Fat Diet ◽  
Acetyl Coa Carboxylase ◽  
High Fat ◽  
Acetyl Coa ◽  
Rice Bran Extract

Altered bone metabolism after high fat diet and exercise: role of Wnt signaling and insulin resistance

2016 ◽  
Author(s):  
Ann-Kristin Picke ◽  
Lykke Sylow ◽  
Lisbeth L V Moller ◽  
Rasmus Kjobsted ◽  
Erik Richter ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Wnt Signaling ◽  
Bone Metabolism ◽  
High Fat Diet ◽  
High Fat ◽  
Diet And Exercise

scholarly journals Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice

2021 ◽  
Vol 137 ◽  
pp. 111370
Author(s):  
Chethan Sampath ◽  
Derek Wilus ◽  
Mohammad Tabatabai ◽  
Michael L. Freeman ◽  
Pandu R. Gangula
Keyword(s):  
Gastric Emptying ◽  
High Fat Diet ◽  
Delayed Gastric Emptying ◽  
High Fat ◽  
Female Mice

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

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