Does Weight Gain Affect Brain Health?

by Nieske Zabriskie, ND

Most people are unaware that the brain plays an important role in regulation of metabolism and appetite. Research shows specific areas in the brain regulate energy intake and expenditure and that brain health impacts body weight.

Weight Regulation in the Brain

There are several hormones, proteins and neurotransmitters that interact within the brain to regulate metabolism and appetite. Research indicates that the melanocortin system in the brain is important for appetite regulation. The peptide pro-opiomelanocortin (POMC) is found in the brain, and studies show that less than optimal synthesis or processing of POMC results in weight gain. Animal models show that lack of the POMC peptide results in excessive eating and early-onset weight gain.¹ POMC also influences dietary preferences, as mice without the POMC peptide show a significant elevation in dietary fat intake. In fact, these mice choose to eat approximately twice as much fat, but similar amounts of carbohydrate and protein, as normal mice.²

Several neuropeptides (short proteins) are orexigenic, meaning that they increase hunger and therefore enhance food consumption. Some of these include ghrelin, orexin, neuropeptide Y and agouti-related peptide. Additionally, low levels of the neurotransmitter serotonin are also associated with excessive hunger and increased food intake. Recent research suggests that the mechanism by which serotonin impacts hunger is through interactions between serotonin receptors and the melanocortin receptors.³ Agouti-related peptide also acts on the melanocortin receptors and preferentially increase intake of a high-fat over a low-fat diet.⁴

Leptin is another protein hormone that functions in weight regulation. Leptin is synthesized in fat tissue and levels of circulating leptin are proportional to the amount of fat in the body. Leptin functions by reducing appetite by inhibiting the synthesis and release of the neurotransmitter neuropeptide Y, which stimulates food intake. Leptin acts primarily by binding to receptors in the hypothalamus, signaling to the brain that current energy stores are sufficient, and thereby regulating energy metabolism. However, individuals with increased body fat have increased leptin levels and become resistant or desensitized to leptin. Leptin also is found in the hippocampus where it plays a role in mood regulation. Animal models show that leptin resistance results in sad mood and behavior.⁵

High-Fat Diet and the Brain

One of the most interesting recent discoveries regarding brain health and energy metabolism is that diet influences areas of the brain that regulate appetite and metabolism. More specifically, eating a high-fat diet can result in an imbalanced inflammatory response in the hypothalamus resulting in suboptimal function. In one study, rodents were fed a high-fat diet similar to the typical Western diet for one day up to 8 months’ duration. The mice and rats consumed nearly double their usual daily amount of calories and gained significant weight. The mice developed an imbalanced inflammatory response in the hypothalamus, which is the part of the brain that controls body weight. Additionally, cells known as glia and microglia accumulated in the hypothalamus and became activated, which is believed to be a protective response to the inflammation. Most importantly, the study showed that the POMC neurons were reduced in number by month 8 of the high-fat diet. The researchers suggested that loss of the POMC neurons may explain why sustained weight loss is so difficult for many individuals.⁶

In another study, rats that were resistant or vulnerable to diet-induced weight gain were fed a high-fat diet and evaluated for changes in brain physiology. The study showed that in the rats vulnerable to diet-induced weight gain, a high-fat diet induced loss of synapses in the POMC nerve cells and a decrease in the connections onto the neighboring neuropeptide Y cells. This study also showed less than optimal health in the central nervous system resulting in decreased accessibility of the POMC and neuropeptide Y cells to blood vessels.⁷ Other rodent studies have shown that high-fat diets result in poor cellular health, decreased neuronal synapses in cells of the hypothalamus,⁸ and suboptimal cerebral circulation and alterations in architecture.⁹

High-fat diets also influence brain-derived neurotrophic factor, which is a protein that supports the survival of existing neurons, and encourages the growth and differentiation of new neurons and synapses. In this study, mice fed a high-fat diet for 7 weeks showed a decrease in the level of brain-derived neurotrophic factor in the hippocampus, decreased number of newly generated cells in the hippocampus, and increased levels of malondialdehyde, a marker of oxidative stress.¹⁰

A similar study evaluated the effects of a short-term high-fat, low-carbohydrate diet on the hypothalamus and hippocampus in rats. The rats showed decreased serotonin release after 1 week and cessation of serotonin release after 6 weeks on the diet. Leptin was increased and changes in insulin receptors were seen as early as 1 week on the diet. The researchers concluded that high-fat diets induce a change in specific central mechanisms involved in energy and glucose homeostasis.¹¹

One study evaluated the impact of a high-fat diet on dopamine levels in the substantia nigra, an area of the brain that regulates movement and coordination. Dopamine, an important neurotransmitter, was found to be lower in the substantia nigra after 5 weeks on a high-fat diet, which correlated to fat mass and suboptimal blood sugar metabolism. Additionally, the substantia nigra showed increased markers of oxidative stress.¹²

Another interesting study examined the combination of a high-fat diet and stress on memory and cognition in rats. After 3 months of the high-fat diet and/or psychosocial stress, the rats showed decreased performance in memory tests. The combination of stress and high-fat diet resulted in more significant and longer-lasting suboptimal memory compared to stress or high-fat diet alone.¹³ A recently published study with human subjects assessed a high-fat, low-carbohydrate diet on brain health. This study showed that compared to the subjects on a standard diet, the high-fat diet for 5 days resulted in less than optimal attention, speed and mood.¹⁴

Studies also indicate that increased visceral fat, which is the fat deposited around the abdominal organs, affects brain health. Multiple large studies have shown that elderly individuals with increased abdominal diameter or fat mass had a significantly higher likelihood of developing suboptimal cognitive function.^15-16 Increased abdominal fat has also been associated with suboptimal brain and hippocampus health, which is the area of the brain important for long-term memory and spatial memory and navigation.^17-18

Natural Products Support Brain Health and Weight Management

It is evident that excess body fat and high-fat diets impact brain health. Individuals with elevated body fat or who are managing their weight therefore may benefit from also supporting brain health through the use of NGF™ (Neuron Growth Factors). NGF includes ingredients to rejuvenate neurites and dendrites in the brain such as acetyl L-carnitine arginate, acetyl L-carnitine, Gotu kola (Centella asiatica), Ginkgo biloba and uridine. Acetyl carnitine and acetyl carnitine arginate increase neurite outgrowth in brain cell cultures and support cognitive function.^19-20 Uridine also stimulates neurite outgrowth as well as blocks receptors that inhibit neurite growth.²¹ Human studies show that Gotu kola supports memory and mood,²² and Ginkgo biloba supports against the effects of free-radicals and enhances neuronal health and blood flow and supports cognitive function.²³

Supporting brain health while also undertaking a weight management regimen can offer a synergistic approach. Weight reduction is important for individuals with excess body fat, particularly individuals with excess abdominal fat deposition. Glycyrrhiza glabra root extract standardized for the bioactive flavonoid glabridin (as in Glabrinex™) can help manage weight. Animal studies demonstrated that overweight mice fed a high-fat diet plus Glycyrrhiza glabra flavonoid oil showed a decrease in body weight gain, weight of abdominal fat tissue, and the size of the fat cells.²⁴ In one study, overweight human subjects were supplemented with 300 mg, 600 mg, or 900 mg of Glycyrrhiza glabra flavonoid oil for 8 weeks. The results revealed that all 3 groups showed a significant reduction in fat mass compared to the levels at the beginning of the study. Furthermore, the group supplemented with the 900 mg per day showed a significant decrease in body weight, body mass index (BMI), and abdominal fat mass.²⁵ Interestingly, research indicates that Glycyrrhiza glabra and glabridin possess properties that contribute to enhancement of neuroprotective activity, memory, learning and mood, and reduction in oxidative stress.^26-28

Modified cellulose and cetylated (esterified) fatty acids (LeptinX™) are also important to support balanced leptin levels. One study found that supplementation with modified cellulose and cetylated fatty acids or placebo in overweight women undergoing a specified diet and exercise plan for 8 weeks resulted in favorable changes in weight and percent body fat as well as reduced leptin levels.²⁹

Conclusion

Researchers are continuing to discover factors that affect brain health, such as eating a high-fat diet. Both increased fat intake and abdominal fat deposition can affect brain health and function. Suboptimal brain health, in turn, can cause imbalances in regulation of the neurotransmitters and neuropeptides that regulate energy metabolism and appetite. Thus, supporting weight management and brain health with natural products can help stop this cycle and optimize health.

References

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