scholarly journals Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet

2009 ◽  
Vol 296 (5) ◽  
pp. E1003-E1012 ◽  
Author(s):  
Kelly A. Posey ◽  
Deborah J. Clegg ◽  
Richard L. Printz ◽  
Jaeman Byun ◽  
Gregory J. Morton ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
Inflammatory Responses ◽  
Neuronal Response ◽  
Caloric Intake ◽  
Reduce Food Intake ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Regulate Food Intake ◽  
The Brain

Weight gain induced by an energy-dense diet is hypothesized to arise in part from defects in the neuronal response to circulating adiposity negative feedback signals, such as insulin. Peripheral tissue insulin resistance involves cellular inflammatory responses thought to be invoked by excess lipid. Therefore, we sought to determine whether similar signaling pathways are activated in the brain of rats fed a high-fat (HF) diet. The ability of intracerebroventricular (icv) insulin to reduce food intake and activate hypothalamic signal transduction is attenuated in HF-fed compared with low-fat (LF)-fed rats. This effect was accompanied by both hypothalamic accumulation of palmitoyl- and stearoyl-CoA and activation of a marker of inflammatory signaling, inhibitor of κB kinase-β (IKKβ). Hypothalamic insulin resistance and inflammation were observed with icv palmitate infusion or HF feeding independent of excess caloric intake. Last, we observed that central IKKβ inhibition reduced food intake and was associated with increased hypothalamic insulin sensitivity in rats fed a HF but not a LF diet. These data collectively support a model of diet-induced obesity whereby dietary fat, not excess calories, induces hypothalamic insulin resistance by increasing the content of saturated acyl-CoA species and activating local inflammatory signals, which result in a failure to appropriately regulate food intake.

scholarly journals Diet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4745-4755 ◽  
Author(s):  
Dana I. Briggs ◽  
Pablo J. Enriori ◽  
Moyra B. Lemus ◽  
Michael A. Cowley ◽  
Zane B. Andrews
Keyword(s):  
Food Intake ◽  
High Fat Diet ◽  
Healthy Aging ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
High Fat ◽  
Appetite Control ◽  
Diet Induced Obesity ◽  
Therapeutic Outcomes ◽  
The Brain

Circulating ghrelin is decreased in obesity, and peripheral ghrelin does not induce food intake in obese mice. We investigated whether ghrelin resistance was a centrally mediated phenomenon involving dysregulated neuropeptide Y (NPY) and agouti-related peptide (AgRP) circuits. We show that diet-induced obesity (DIO) (12 wk) suppresses the neuroendocrine ghrelin system by decreasing acylated and total plasma ghrelin, decreasing ghrelin and Goat mRNA in the stomach, and decreasing expression of hypothalamic GHSR. Peripheral (ip) or central (intracerebroventricular) ghrelin injection was able to induce food intake and arcuate nucleus Fos immunoreactivity in chow-fed but not high-fat diet-fed mice. DIO decreased expression of Npy and Agrp mRNA, and central ghrelin was unable to promote expression of these genes. Ghrelin did not induce AgRP or NPY secretion in hypothalamic explants from DIO mice. Injection of NPY intracerebroventricularly increased food intake in both chow-fed and high-fat diet-fed mice, indicating that downstream NPY/AgRP neural targets are intact and that defective NPY/AgRP function is a primary cause of ghrelin resistance. Ghrelin resistance in DIO is not confined to the NPY/AgRP neurons, because ghrelin did not stimulate growth hormone secretion in DIO mice. Collectively, our data suggests that DIO causes ghrelin resistance by reducing NPY/AgRP responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis to limit further food intake. Ghrelin has a number of functions in the brain aside from appetite control, including cognitive function, mood regulation, and protecting against neurodegenerative diseases. Thus, central ghrelin resistance may potentiate obesity-related cognitive decline, and restoring ghrelin sensitivity may provide therapeutic outcomes for maintaining healthy aging.

scholarly journals Increased Food Intake Leads to Obesity and Insulin Resistance in the Tg2576 Alzheimer’s Disease Mouse Model

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1532-1540 ◽  
Author(s):  
Motoyuki Kohjima ◽  
Yuxiang Sun ◽  
Lawrence Chan
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Food Intake ◽  
Mouse Model ◽  
Feeding Behavior ◽  
Neurotrophic Factor ◽  
Caloric Intake ◽  
Brain Derived Neurotrophic Factor ◽  
Normal Diet ◽  
The Brain

Recent studies suggest that hyperinsulinemia and insulin resistance are linked to Alzheimer’s disease (AD). In this study, we used Tg2576 transgenic (Tg) mice, a widely used transgenic mouse model for AD, to explore the relationship between increased amyloid β-peptide (Aβ) and insulin resistance. When fed a high-fat diet (HFD), Tg mice developed obesity and insulin resistance at 16 wk of age. Furthermore, HFD-fed Tg mice displayed abnormal feeding behavior and increased caloric intake with time. Although caloric intake of HFD-fed Tg mice was similar to that of normal diet-fed Tg or wild-type mice during 4 to 8 wk of age, it increased sharply at 12 wk, and went up further at 16 wk, which paralleled changes in the level of Aβ40 and Aβ42 in the brain of these mice. Limiting food intake in HFD-fed Tg mice by pair-feeding a caloric intake identical with that of normal diet-fed mice completely prevented the obesity and insulin intolerance of HFD-fed Tg mice. The hypothalamus of HFD-fed Tg mice had a significant decrease in the expression of the anorexigenic neuropeptide, brain-derived neurotrophic factor, at both the mRNA and protein levels. These findings suggest that the increased Aβ in the brain of HFD-fed Tg2576 mice is associated with reduced brain-derived neurotrophic factor expression, which led to abnormal feeding behavior and increased food intake, resulting in obesity and insulin resistance in these animals.

scholarly journals Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity

2019 ◽  
Author(s):  
Lisa Y. Beppu ◽  
Xiaoyao Qu ◽  
Giovanni J. Marrero ◽  
Allen N. Fooks ◽  
Adolfo B. Frias ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
High Fat Diet ◽  
Caloric Intake ◽  
Transcriptional Regulator ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Visceral Adipose

ABSTRACTCrosstalk between the immune system and adipocytes is critical for maintaining tissue homeostasis and regulating chronic systemic inflammation during diet-induced obesity (DIO). How visceral adipose tissue resident regulatory T cells (aTregs) signal to adipocytes in the visceral adipose tissue (VAT) is not understood. Here we show that Treg-specific ablation of the transcriptional regulator Blimp-1 resulted in increased insulin sensitivity, decreased body weight and increased Ucp-1 in adipocytes in high fat diet (HFD)-fed mice. Mechanistically, we demonstrate that Blimp-1 drives IL-10 production in Tregs, thus suppressing beiging and energy expenditure in adipocytes. Moreover, IL-10 mRNA expression positively correlated with increasing body weight in humans. These findings reveal a surprising relationship between aTregs and adipocytes in promoting insulin resistance during excessive caloric intake, placing Blimp-1-regulated IL-10 expression by aTregs at a critical juncture in the development of obesity and its associated comorbidities in mice and humans.SUMMARYHere we show that ablation of Blimp-1 in adipose tissue resident Tregs (aTregs) leads to decreased IL-10 production, resulting in increased Ucp-1 expression and beiging by adipocytes and protection from diet-induced obesity and insulin resistance.

scholarly journals Prenatal influences on leptin sensitivity and susceptibility to diet-induced obesity

2006 ◽  
Vol 189 (2) ◽  
pp. 355-363 ◽  
Author(s):  
Stefan O Krechowec ◽  
Mark Vickers ◽  
Arieh Gertler ◽  
Bernhard H Breier
Keyword(s):  
Food Intake ◽  
High Fat Diet ◽  
Adult Life ◽  
Female Offspring ◽  
Leptin Resistance ◽  
Reduce Food Intake ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Ad Libitum

Obesity and type 2 diabetes are world wide health issues and their incidence is rapidly increasing. Currently the biological factors responsible for the development of obesity are only partially understood. Recent research has shown that maternal nutrition during pregnancy may have long-term metabolic consequences in offspring. In the present study we investigated interactions between prenatal and postnatal nutrition on leptin sensitivity and obesity development. Wistar rats were time-mated and randomly assigned to either ad-libitum (AD) or to 30% of ad-libitum (UN) food intake throughout pregnancy. After weaning, female offspring were fed standard chow, a high-fat diet or a calorie restricted diet. Female offspring of UN dams were growth retarded at birth and showed increased susceptibility to diet-induced obesity on a high-fat diet. At 142 ± 5 days of age, leptin sensitivity was measured as a response to 14 days of leptin treatment (2.5 μg/g/day, s.c.). In UN offspring fed chow, leptin treatment failed to reduce food intake and weight loss was diminished. This leptin resistance observed in UN offspring was independent of diet-induced obesity and was associated with fasting hyperinsulinemia and hypertriglyceridemia. Our study suggests that prenatal nutrition can shape future susceptibility to obesity through alterations in leptin sensitivity and changes in energy metabolism during adult life.

scholarly journals High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

2021 ◽  
Vol 22 (7) ◽  
pp. 3746
Author(s):  
Ilaria Zuliani ◽  
Chiara Lanzillotta ◽  
Antonella Tramutola ◽  
Eugenio Barone ◽  
Marzia Perluigi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Mitochondrial Activity ◽  
High Fat ◽  
Hexosamine Biosynthetic Pathway ◽  
Neurodegenerative Process ◽  
The Brain

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.

scholarly journals Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance

2016 ◽  
Vol 310 (9) ◽  
pp. F812-F820 ◽  
Author(s):  
Jonathan M. Nizar ◽  
Wuxing Dong ◽  
Robert B. McClellan ◽  
Mariana Labarca ◽  
Yuehan Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
High Fat ◽  
Electrolyte Excretion ◽  
Diet Induced Obesity ◽  
Collecting Ducts ◽  
Fat Feeding

The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na+-sensitive hypertension, and prior studies have proposed a role for the epithelial Na+ channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na+ reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na+ excretion and elevated blood pressure, which was significantly higher on a high-Na+ diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na+ transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na+ diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na+-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na+ reabsorption upstream of the aldosterone-sensitive distal nephron.

Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Black Rice ◽  
High Fat ◽  
Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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