Weight Loss Plateaus, Leptin Resistance, and Brain Inflammation

August 29, 2016 | Linda J. Dobberstein, Chiropractor, Board Certified in Clinical Nutrition

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Weight Loss Plateaus, Leptin Resistance, and Brain Inflammation
When it comes to weight loss, inevitably there is a plateau. Sometimes this plateau happens at an appropriate body weight, but other times it happens prematurely. Weight and blood sugar levels may not budge despite doing everything right. Staying at this plateau is frustrating, heart-breaking and may even seem like defeat. There are numerous factors that play a role in weight loss plateaus.

One of the most important factors relates to how well leptin is communicating to the hypothalamus in the brain. New understandings of chronic, low-grade brain and hypothalamic inflammation define how well the leptin hormone functions. When this is not working right, central leptin resistance occurs which leads to metabolic syndrome, diabetes, obesity, cardiovascular disease, and weight loss plateaus. Understanding and implementing tools pertaining to chronic low-grade hypothalamic brain inflammation may help you break through stubborn road blocks in weight management.

[Jump to: Nutritional Options]

Central Leptin Resistance and Brain Inflammation


Central leptin resistance is the result of the hypothalamus in the brain failing to recognize and use high levels of leptin in the brain. This condition results in obesity and other metabolic changes. Ongoing recent research provides solid information that chronic low level inflammation affects the hypothalamus, the mitochondria, and endoplasmic reticulum (another organelle or structure inside cells) of the brain. Mitochondria are little organelles or factories inside cells that burn fat and sugar to produce energy. The endoplasmic reticulum (ER) is a mini-factory inside cells that manufactures and packages proteins and works closely with RNA.

The hypothalamus is part of the brain’s limbic system and is the headquarters for regulating daily, fundamental physiological activities. The hypothalamus regulates metabolism, energy production, calorie and nutrient sensing, appetite control, energy expenditure, carbohydrate and fat metabolism. Leptin, insulin, ghrelin, cholecystokinin, and circulating nutrients talk to the hypothalamus. They give feedback and receive direction from the hypothalamus.

Chronic Low Grade Inflammation


Scientists know that under certain conditions, the hypothalamus, the command center for daily physiology, gets terribly stressed from either acute, severe inflammation like an acute overwhelming infection or wasting away from severe cancer. The hypothalamus also gets stressed with low-grade chronic inflammation. Scientists believe low level inflammation in the brain and hypothalamus causes metabolic syndrome, diabetes, and heart disease.

This inflammation is unique as compared to inflammation as we know it like a sprained ankle. It’s not visible. This type of brain inflammation is termed metainflammation. It is defined as “low-grade, chronic inflammation occurring at molecular levels and is orchestrated by metabolic cells in response to excess nutrients and energy.” It leads to central leptin resistance or high levels of leptin in the brain unable to communicate to the hypothalamus. The hormones are present in the brain in high amounts but because the command center is inflamed, the hormones aren’t getting through.

Causes of Hypothalamus Inflammation or Metainflammation


Hypothalamic inflammation, or metainflammation, is set off by a number of causes. High intake of fat and sugar in the diet is one of the major modern causes of central leptin resistance. It can happen after a brief indulgence or be a result of chronic exposure. Researchers found that inflammation in the brain from a high fat, high sugar, low nutrient diet can occur within a few hours up to three days after an acute (one-time/ short- term) exposure.

When this type of food intake is sustained, it is thought that it causes the hypothalamus to stay chronically inflamed or sprained. This affects leptin and insulin signaling which then causes energy metabolism to be compromised and leads to the development of obesity, diabetes, and cardiovascular disease. The metainflammation is the root of the disease and is present before obesity occurs. This reflects not only how fit is your fat, but how fit is your diet and your hypothalamus.

Other identified causes of inflammation affecting the hypothalamus may stem from disruption of the gut microbiome or the intestinal tract flora. Certain gut bacteria determine caloric intake from foods further impacting the diet’s effect on brain health or inflammation.

Metainflammation also affects how the mitochondria and the endoplamsmic reticulum (ER). These are organelles or little structures inside cells that play very significant roles in metabolism. Loss of sleep or impaired sleep affects these organelles significantly and further impacts the hypothalamus leading to high levels of leptin, leptin resistance, and hypothalamic inflammation. Disrupted sleep affects how the endoplasmic reticulum is able to do its manufacturing and shipping job, i.e. less repair with a higher level of inflammation occurs.

Mitochondrial dysfunction and sleep deprivation impairs hypothalamic function, increases inflammation in the brain, impairs energy production and alters blood sugar and fat burning. Thus, sleep disruption causes major stress and metainflammation. It is a major reason for sugar cravings and increased carbohydrate intake.

Chronic stress and removal of the ovaries were also found to create central leptin resistance. Brain, leptin, and hypothalamic stress occurred because of the molecular inflammation and loss of the hormonal protective effects.

Hypothalamic Inflammation Affects Thyroid and Adrenal Glands


When the hypothalamus is inflamed, research shows that it affects other pathways like how the brain communicates to the thyroid (HPT axis) and adrenal glands (HPA axis). This causes stressed thyroid and adrenal function leading to inefficient, stressed metabolism and weight gain. It is not a thyroid or adrenal problem directly at the gland level in that the gland is pathologically damaged. Rather, it is the communication system between the brain and the gland(s) that is stressed and not functioning optimally.

How to Improve Central Leptin Resistance and Hypothalamic Inflammation


The fallout of this metainflammation, hypothalamic inflammation, and central leptin resistance is widespread, but there are ways of quenching this damaging metabolic disturbance. The most fundamental approach to reducing hypothalamic inflammation is to eat a nutrient dense diet. Remove high intake of carbohydrate/ sugar-rich foods and low quality fats (like trans-fat, excessive low quality saturated fats, and reduce vegetable oils). Increase the amount of protein to half of your ideal body weight in total grams of protein per day.

Many health professionals recommend to eat every three hours to keep metabolism and blood sugar levels elevated. However, in doing so, it is oversupplying nutrition to the hypothalamus. This is especially true when a sedentary lifestyle and high calorie nutrient poor foods are in the picture. It’s a recipe for metainflammation. Eating three meals per day with no snacks, per the Leptin Diet, is a more ideal way to eat to improve leptin hormone function and weight loss.

Quality sleep is essential for the brain to manage molecular inflammation and nerve cell repair. Following the natural light-dark circadian rhythms is integral for metabolic rhythm and leptin function.

Nutritional Support for Brain Inflammation and Central Leptin Resistance


A clinical trial study published August 2016 in the American Journal of Clinical Nutrition evaluated the omega-3 nutrients DHA comparing it to EPA for its role in modulating inflammation, including IL-6. Interleukin-6 or IL-6 is one of many compounds involved with inflammation management and leptin.

In this double-blind, randomized, crossover, controlled study, men and women were given trials of EPA at 2.7 grams per day, DHA at 2.7 grams per day, and corn oil at separate intervals with time between the treatment periods. DHA supplementation significantly surpassed the EPA benefits. The control group results with the corn oil were not mentioned in the study’s abstract.

Results for the DHA supplementation showed significant reduction inflammation with C-Reactive Protein (CRP), Tumor Necrosis Factor (TNFa), and improvements in IL-6. Triglycerides, cholesterol to HDL ratio, HDL, and LDL cholesterol levels also improved. Omega-3 DHA is essential for the normal structure of brain and cell membranes, but it is integral to managing IL-6 and inflammation in the brain.

The herb ashwagandha was found in recent animal studies to stabilize mitochondrial function and prevent inflammatory stress to the hypothalamus in diabetic rats. Protecting mitochondria and delicate nerve tissue is central to healthy metabolism.

Several other nutrients and food compounds have been identified to help restore leptin sensitivity by supporting nerve tissue response. The nutrients identified are resveratrol, green tea extract, caffeine, and taurine. A review study found these compounds able to reverse leptin resistance and reduce compounds that increased appetite. Some of the compounds, like vitamins A and D, support leptin transport into the brain.

Green tea extract has been shown to reduce the effect of high fat diets and modulate several inflammatory compounds affecting hypothalamic inflammation. Researchers suggested that tea saponin from green tea provide promising results as an anti-obesity and anti-inflammatory agent with central leptin resistance. After just 21 days, animals that were give 10 mg per kilogram daily of tea saponins found improvement in hypothalamic inflammation and central leptin resistance.

A study published in the journal Nutrition studied the effect of passion flower on the sensation of feeling full or satisfied in this animal study. Animals were fed a high fat, high calorie diet to cause obesity. The group treated with passion flower, had improved insulin sensitivity, increased the rate at which glucose was used up, and improved satiety.

The amino acid acetyl-l-carnitine provides multiple benefits in this context of brain inflammation, mitochondria stress, leptin, and the symptom of depression that often accompanies obesity. A July 2016 study evaluated the use of acetyl-l-carnitine in helping depression, obesity, insulin, blood sugar, and leptin. It was found to be highly favorable in helping reduce depression, oxidative stress, and inflammation in the brain, while helping insulin and blood sugar work well. It was considered very helpful in treatment- resistant depression and obesity.

The amino acid taurine has been shown to preserve and protect the hypothalamus in animal studies. Researchers fed mice a protein-restricted diet or their baseline diet, but in the context of a high-fat diet. The effect of taurine on metabolism was widespread and complex. Changing the diet to reduction of fat and excess calories with taurine supplementation supported the hypothalamus, cell defense, endoplasmic reticular stress, and cellular repair.

Restoration of the gut microbiome with healthy gut bacteria and removing the non-beneficial bacteria provides another approach to supporting the brain. Protecting the mitochondria is important. Numerous compounds protect these essential energy producing organelles. These include coenzyme Q10, acetyl-l-carnitine, B vitamins, curcumin, quercetin, PQQ, resveratrol, and astaxanthin.

Central leptin resistance and hypothalamic inflammation can be managed and quenched. Those who have reached plateaus in weight loss must address this inflammation with nutrition, behavioral, and dietary changes. Nutrient dense diets, good sleep, and nutrients like DHA, ashwagandha, green tea extract, acetyl-l-carnitine, passion flower, and taurine provide support for the hypothalamus and metainflammation. Don’t let leptin resistance defeat you. Use this information to charge of your health.

Nutritional Options


DHA – The omega-3 fish oil DHA provides essential benefits to numerous tissues and functions in the body. The American Journal of Clinical Nutrition nicely outlined the superiority of DHA over EPA for inflammation reduction. DHA fish oil supports healthy brain function, cholesterol management, and is integral to the physical structure of the brain.

Ashwagandha – Ashwagandha is an adaptogenic herb commonly used to help stress tolerance. It is often used to support healthy thyroid hormone function. Research shows that it protects and helps the hypothalamus and mitochondria in times of dietary and metabolic stress even in the context of blood sugar imbalances.

Green Tea Extract – Green tea contains a number of antioxidants like ECGC and tea saponins. Tea saponins have been shown to help blood sugar, obesity, and reduce hypothalamic inflammation.

Acetyl-L-Carnitine – This amino acid helps mitochondria function. Research shows acetyl-l-carnitine provides key support for those who struggle with the entanglement of obesity and depression.

Passion Flower Extract – This natural plant compound is often used to help with sleep, stress, anxiety, and insomnia as it helps the brain make the relaxant neurotransmitter, GABA. Research shows that it helps with feeling more satisfied from food. Passion flower may be used during times of stress eating or a poor diet. It helps with blood sugar management.

Taurine – This natural amino acid has been shown to affect hypothalamic inflammation. It is a calming amino acid that is also protective to cell membranes, oxidative stress, detoxification, electrolyte management, blood sugar, kidney and heart function.

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