Polyphenol-rich virgin olive oil reduces insulin resistance and liver inflammation and improves mitochondrial dysfunction in high-fat diet fed rats

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance and metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism is not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed decreased blood glucose and serum insulin and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which are induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the addition of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate-induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element-binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.

Download Full-text

132 Mitochondrial dysfunction preceeds insulin resistance in skeletal muscle of mice fed high fat diet

Mitochondrion ◽

10.1016/j.mito.2009.12.123 ◽

2010 ◽

Vol 10 (2) ◽

pp. 237 ◽

Cited By ~ 1

Author(s):

Sihem Boudina ◽

Sandra Sena ◽

Robert C. Cooksey ◽

Deborah Jones ◽

Donald A. McClain ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

High Fat

Download Full-text

Palmitoleic Acid (N-7) Attenuates the Immunometabolic Disturbances Caused by a High-Fat Diet Independently of PPARα

Mediators of Inflammation ◽

10.1155/2014/582197 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 26

Author(s):

Camila O. Souza ◽

Alexandre A. S. Teixeira ◽

Edson A. Lima ◽

Helena A. P. Batatinha ◽

Lara M. Gomes ◽

...

Keyword(s):

Insulin Resistance ◽

Oleic Acid ◽

High Fat Diet ◽

Palmitoleic Acid ◽

Serum Levels ◽

Standard Diet ◽

Liver Inflammation ◽

Wild Type ◽

High Fat

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-αdependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF𝜅B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.

Download Full-text

Protective effects of phyllanthin, a lignan from Phyllanthus amarus, against progression of high fat diet induced metabolic disturbances in mice

RSC Advances ◽

10.1039/c6ra10774e ◽

2016 ◽

Vol 6 (63) ◽

pp. 58343-58353 ◽

Cited By ~ 11

Author(s):

Sneha Jagtap ◽

Pragyanshu Khare ◽

Priyanka Mangal ◽

Kanthi Kiran Kondepudi ◽

Mahendra Bishnoi ◽

...

Keyword(s):

Insulin Resistance ◽

Lipid Peroxidation ◽

Glucose Metabolism ◽

High Fat Diet ◽

Phyllanthus Amarus ◽

Protective Effects ◽

Liver Inflammation ◽

High Fat ◽

Metabolic Disturbances ◽

Induced Changes

Phyllanthin delayed the progression of high fat diet induced changes affecting lipid and glucose metabolism such as adiposity, hypertriglyceridemia, fatty liver, inflammation, lipid peroxidation and insulin resistance.

Download Full-text

Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats

Journal of Endocrinology ◽

10.1530/joe-18-0552 ◽

2019 ◽

Vol 241 (1) ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Jirapas Sripetchwandee ◽

Hiranya Pintana ◽

Piangkwan Sa-nguanmoo ◽

Chiraphat Boonnag ◽

Wasana Pratchayasakul ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Cognitive Decline ◽

Mitochondrial Dysfunction ◽

Dendritic Spine ◽

High Fat Diet ◽

High Fat ◽

Long Term Depression ◽

Impaired Insulin

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.

Download Full-text