How metabolic syndrome interacts with stress – mouse model

Emory researchers recently published a paper in Brain, Behavior and Immunity on the interaction between psychological stress and diet-induced metabolic syndrome in a mouse model.

“The metabolic vulnerability and inflammation associated with conditions present in metabolic syndrome may share common risk factors with mood disorders. In particular, an increased inflammatory state is recognized to be one of the main mechanisms promoting depression,” writes lead author Betty Rodrigues, a postdoc in Malu Tansey’s lab in the Department of Physiology.

This model may be useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders. As a follow-up, Tansey reports that her team is investigating the protective effects of an anti-inflammatory agent on both the brain and the liver using the same model.

Metabolic syndrome and stress have a complex interplay throughout the body, the researchers found. For example, psychological stress by itself does not affect insulin or cholesterol levels, but it does augment them when combined with a high-fat, high-fructose diet. In contrast, stress promotes adaptive anti-inflammatory markers in the hippocampus (part of the brain), but those changes are wiped out by a high-fat, high-fructose diet.

The findings show synergistic effects by diet and stress on gut permeability promoted by inflammation, and the biliverdin pathway. Biliverdin, a product of heme breakdown, is responsible for a greenish color sometimes seen in bruises.

“Stress and high-fat high-fructose diet promoted disturbances in biliverdin, a metabolite associated with insulin resistance,” Rodrigues writes. “To the best of our knowledge, our results reveal for the first time evidence for the synergistic effect of diet and chronic psychological stress affecting the biliverdin pathway.”

In this mouse model, previously developed in cooperation with Gretchen Neigh, stress is imposed by putting mice in a plastic ball 5 inches wide, and then placing the mobile ball in a cage with a large aggressive rat for 15 minutes every day for two weeks. The mouse can see, hear and smell the rat, but direct physical contact is not permitted. Some of the mice are fed a Western diet: food consisting of 42 percent fat by calories, supplemented with 30 percent fructose to drink.

Rodrigues also notes effects of diet and stress on the adipokine Lcn2, writing: “Recent human studies have positively correlated increased circulating Lcn2/NGAL with anxiety and depression. This association seems particularly apparent in states of chronic metabolic imbalance such as in late life depression or chronic heart failure.”

Related research at Emory:

Gretchen Neigh’s investigations, with Constance Harrell, on fructose + stress (note: Neigh is now at Virginia Commonwealth University)

Saul Karpen’s work on fatty liver disease + bile acids

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Posted on by Quinn Eastman in Heart, Immunology, Neuro Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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