Rat study links flavonoids to less depression among offspring of overfed mothers

The study was conducted by a group of researchers associated with several Mexican universities and institutes.  It was published earlier this month in the journal Nutrients.​

Obesity is a topic of critical importance in Mexico.  By some measures the country is now the most obese in the world.

Obesity linked to lifestyle diseases

Obesity is often thought of as one of the primary risk factors for developing a host of lifestyle related disease, including cardiovascular disease, stroke, kidney problems and type 2 diabetes.  Obese individuals also suffer from depression at a higher rate, but the connection here is less clear than with the physiological manifestations.  In the United States, the Centers for Disease Control found that 43% of adults with depression were obese, and adults with depression were more likely to be obese than adults without depression.  But a recent Mexican study​​ found while that women who were obese were 1.28 times more likely to also suffer from depression, no such correlation was found for obese men.

A 2014 study published in the journal Psychosomatic Medicine​​ found general support for the notion that Major Depressive Disorder  (MDD) and obesity were linked in families. But the authors said that in a surprising result, they did not find that obese mothers were more likely to give birth to babies at greater risk of MDD.  The authors of that study said this was, “a finding that requires further investigation.”​

Obesity-depression link more clear in animal models

But the authors of the Nutrients​ study said in animal models this relationship is more straightforward, which lends credence to the idea that some underlying biochemical processes are at work.  Accurately assessing depression rates in humans is complicated by cultural factors.

“Hyper caloric diet exposure, such as high fat diet (HFD), cafeteria diet (CAF), and high sugar diet (HSD), intake in rodents programs offspring to show long-term behavioral defects later in life, including anxiety, autism, addiction-like, and depression-like behavior . Potential molecular changes on these scenarios are associated with the disruption of dopamine and opioid neurotransmission in the nucleus accumbens and the prefrontal cortex, increased circulating corticosterone plasma levels, oxidative stress and peripheral and central inflammation,” ​the authors of the recent rat study wrote.

In the Nutrients​ study​​, the researchers looked at the effect of two flavonoids: kaempferol-3-O​-glucoside and narirutin.  Although these compounds are rarely extracted as dietary ingredients, the researchers said they are widely distributed in the plant kingdom, being present in the genuses Citrus, Brassica, Allium​ (onions and garlic), and Malus ​(apples).​ The researchers noted the two compounds are found together in grapefruit extract, though they used test materials purchased from Sigma Aldrich.

Diets mimic worst aspects of Western diet

The researchers fed the rats four different diets:  a standard chow, a high fat diet, a ‘cafeteria’ diet (meaning the rats could eat as much as they wanted) that mimics some of the lesser aspects of the Western diet including bacon, liquid chocolate and fried potatoes, and a high sugar diet.  They also used a cafeteria diet supplemented with supplemented with the flavonoids, kaempferol-3-O​-glucoside at 15 mg/kg bw and narirutin  at 30 mg/kg bw.

The rats were divided into the groups and fed the various diets.  The researchers then fed the offspring of those rats the same diets and, after 21 days of lactation, derived four groups from the offspring (about 16 animals in each group) and fed them these same diets for another five weeks, at which time the depression rates were measured.

Depression was measured with a force swim test, a validated method in this model. Rats that are depressed give up sooner, is the basic idea. The rats were then sacrificed and tissue collected from the prefrontal cortex and the hippocampus.

The rats that were supplemented with the flavonoids both swam longer and showed increased climbing activity (where they attempt to climb the walls of the enclosure to escape the water).  The researchers concluded that, “[C]afeteria diet intake leads to substantial depressive-like behaviour, which is fully prevented by flavonoids supplementation. Our data supports the potential protective role of flavonoids on defective behaviour programmed by maternal obesity during the perinatal period.”​

Source: ​Nutrients​​​
Maternal Flavonoids Intake Reverts Depression-Like Behaviour in Rat Female Offspring
11​(3), 572; doi:10.3390/nu11030572
Authors: De la Garza AL, et al.