The Role of Inflammation in Body Weight: An Intro to the Biology of Fat

Inflammation comes up a lot in my practice. It promotes many chronic diseases and correlates with worsening signs and symptoms of many conditions, whether it be autoimmune disease, arthritis, cardiovascular disease, or others. Inflammation is also intrinsically tied to obesity.  How are inflammation and body weight related and what can we do about it?

What is inflammation?

Inflammation is your body’s attempt to protect itself. It involves complex biological processes that are activated by things like foreign invaders (bacteria and viruses for example) or damaged cells (injury). We need inflammation to protect ourselves from these harmful stimuli and to initiate healing, but we want this inflammation to resolve. When it doesn’t, or there is always a stimulus promoting inflammation, we get chronic inflammation. Chronic inflammation is associated with chronic diseases like autoimmune disease, atherosclerosis, cancer, HIV/AIDS, allergies, and has even been connected to the pathophysiology of depression.  Chronic inflammation can lead to and exacerbate cardiovascular disease, insulin resistance, and a host of other problems. It is also an important feature of obesity.

The Many Roles of Fat 

Our fat cells are more than just energy storage. They are a vital part of the endocrine system. We NEED our fat cells (adipocytes) to help regulate insulin sensitivity, for sex hormone production, to insure a functioning immune system, and regulate metabolism through hormones associated with the fat cells themselves (adiponectin and leptin are the most studied, resistin is another).Adiposity

Adiponectin

Adiponectin is an important metabolism hormone, enhancing insulin sensitivity of skeletal muscle and the liver, helping clear glucose from the blood stream. Adiponectin decreases as body weight increases resulting in increased insulin resistance with weight gain. (1) There are genetic reasons for low adiponectin levels as well that are known to increase the risk of type 2 diabetes. (2)

Adiponectin ties in to inflammation in part with vascular disease. Adiponectin inhibits a cell signaling protein involved in inflammation called TNF-α and affects plaque formation in the arteries. It does this by inhibiting the conversion of immune cells called macrophages to foam cells which are implicated in plaque buildup in the arteries. (3) In general, higher adiponectin levels are associated with lower body weight, better blood sugar control, and reduced inflammation, particularly in blood vessels.

Raising Adiponectin Levels

Your adiponectin levels are in part regulated by genetics but there are things you actually can do to raise adiponectin levels. Eating a diet high in fiber, getting plenty of omega-3s, exercise, and weight loss have all been shown to raise adiponectin levels. (4)

Leptin

Leptin is another hormone secreted by fat cells and is most known for suppressing hunger signals, but it has many other interesting effects as well. These include influences on the immune system, metabolism, bone and blood vessel formation, and reproduction.

Leptin levels directly correlate with the amount of energy stored in the adipose tissue. In obesity more leptin is secreted because there is more adipose tissue. Based on this you might expect heavier people to have less hunger, but we know this isn’t true. The reason obese people still have strong hunger signals is because there is a mechanism at play reducing the sensitivity of cells to leptin’s actions so its impacts on satiety are blunted.

High Leptin –> Elevated Immune Response –> Elevated Inflammation

The elevated level of circulating leptin in obesity contributes to low-grade chronic inflammation by upregulating inflammatory cytokines (like TNF, IL-12, and IL-6). Leptin levels also increase when there is other inflammatory stimulus, further increasing inflammation, (5) and has many other effects on both major immune system branches known as adaptive and innate immunity. Leptin’s influence on the immune response is also apparent when there are low levels, which leads to an impaired immune system—not producing an inflammatory response when you do want it. (6)

Elevated leptin levels and the associated elevation in inflammation are almost always associated with an elevated BMI.

What can we do to improve leptin sensitivity?

When weight is lost and leptin levels decline hunger signals increase. This is one of the reasons sustained weight loss is challenging, so finding ways to improve leptin sensitivity may improve outcomes of weight loss attempts.

  • Improve triglyceride levels. Triglycerides are fats that are often associated with heart disease. They are a standard part of your cholesterol blood work. Having high triglycerides can induce leptin resistance. (7) Things that can help lower triglycerides include weight loss, exercise, a low carbohydrate diet, reducing alcohol consumption, and not smoking.
  • Because leptin is associated with a feeling of fullness, doing other things to help you feel full like eating protein and healthy fats with each meal or snack can help create a more sustained blood sugar and curb hunger.
  • Reduce total body inflammation because inflammation signals to the brain appear to be an important factor in leptin resistance. (8) I’ll discuss more on this later.

Resistin

Resistin is another adipose-derived hormone that appears to have a strong role in the pathogenesis of cardiovascular disease, type 2 diabetes, and inflammation. It is actually primarily secreted by macrophages but is also secreted by fat cells and is associated with the inflammation associated with fat. It promotes endothelial cell dysfunction (the cells lining blood vessels and lymphatic), increasing multiple pro-inflammatory mediators.

Reducing resistin

  • Antioxidants – Studies have shown resistin can be reduced by consuming antioxidants like vitamin C, which you can get from your diet from eating fruits and vegetables.(9)
  • Optimize Folate Levels – Folate has been shown to improve not only endothelial cell dysfunction, but also reduce homocysteine (which, when elevated is associated with atherosclerosis), as well as reduce resistin itself.(10)
  • Olive oil may also be beneficial. Oleic acid, the primary fat in olive oil, was shown to reduce DNA expression of the resistin gene in fat cells.(11)

Macrophage Phenotypes

The following paragraphs get pretty science-y, so buckle up, or skip it.

A macrophage is an immune cell that I like to picture as Pac-Man, gobbling up inflammatory debris. For those of you paying attention, you may be saying, “Wait! Didn’t you say macrophages release resistin and can promote inflammation?!” Yes. They play a very interesting role in inflammation and obesity, being beneficial in some cases and inflammation-inducing in others.

I will explain (with the caveat that this is a bit of an over-simplification):

Macrophages come in 2 major types, M1 and M2 (with subsets of the M2 form), and they do different things. M1 is thought of as pro-inflammatory while M2 is associated with anti-inflammatory reactions. (12) Obesity pushes the balance to be M1-predominant resulting in more inflammation. (13)

What do you do to improve macrophage phenotype to M2?

More recently discovered compounds called resolvins, which are constituents of omega-3s, show promise as a potential therapy because they recruit macrophages. Not only that, resolvins and its precursor, DHA, actually promote the M2 phenotype which suppresses Th2 inflammation and fibrosis. (14) (15)

Researchers have indeed proposed that resolvins may be a potential treatment for obesity-associated inflammation but more research is necessary to determine the extent of its therapeutic application. In phase 2 clinical trials side effects have not been documented. Caution should be used however because macrophages do accumulate in obesity, especially with lymphatic impairment because a functioning lymphatic system is necessary to move these immune cells away from the periphery so they don’t accumulate and potentially cause damage. There may still be benefit due to the changes to an M2 phenotype as mentioned above, but it is still best if a healthcare provider determines if this may be an appropriate treatment on an individual basis.

Higher adiponectin can also promote M2 macrophages, so see above for ways to improve adiponectin levels.

Decreasing Total Body Inflammation

Because so many chronic conditions are caused or exacerbated my inflammation, trying to decrease chronic inflammation is important.

One way to reduce inflammation associated with obesity probably goes without saying—lose weight and inflammation will likely decline. (16) In the meantime there are other things you can do as well.

Fat cells themselves aren’t the only source of inflammation in the body and because inflammation can contribute to so many different chronic conditions, identifying other causes of inflammation and correcting this excessive immune response is important.

  • Eliminate or greatly reduce added sugar – Sugar is ubiquitous in the standard American diet. Some obvious like soda, baked goods, and candy, but some less obvious like added sugars in yogurt, pasta, crackers, and sauces.  For many cutting sugar can be incredibly challenging. I find eliminating all added sugars for 14 days is rather effective at reducing or eliminating sugar cravings in many people. For others it is better to identify personal obstacles and individualize a plan to decrease sugar consumption. The American Heart Association and the American Diabetes Association recommend limiting added sugars to below 25 grams daily
  • Address allergies – This includes identifying food allergies and sensitivities and removing them from the diet either through an elimination/re-challenge diet or testing, as well as addressing environmental allergies.
  • Eat plants – Plants contain many different compounds such as polyphenols that help reduce oxidative damage in the body. Eating a rainbow of colors can help you get many different types of these phytonutrients.Phytonutrients
  • Other dietary strategies – Choose a diet that is right for you that also has anti-inflammatory benefits. The Mediterranean diet is generally a good dietary strategy for most people and has been shown to have numerous benefits on cardiovascular risk markers such as inflammation. It has even been shown to change the way DNA is expressed of several inflammation-related genes. (17)  It is characterized by healthy fats like those from olive oil, nuts and seeds, poultry, eggs, seafood, whole grains, and lots of colorful fruits and vegetables.  Some people may benefit from other diets such as the ketogenic/high fat low carb diet or certain dietary strategies such as intermittent fasting (limited eating window) for example. Consult your healthcare provider to help determine the diet that is right for you
  • Stress reduction – The “stress hormone” cortisol causes increased inflammation after acute stressors, whether it be a vicious animal chasing you or sitting in traffic. It does this to get your body’s immune system prepared to repair or defend.  In modern society we tend to have many low-grade stressors (i.e. getting the kids to the bus stop on time, that presentation you have to give, paying bills, etc) resulting in a lot of signals to increase inflammation. Meditation, breathing techniques, and even intermittent fasting can improve your response to stress
  • Optimize Sleep – Your sleep is very important for proper immune system function and getting poor sleep, especially over a long period of time is another chronic stressor. Also included would be addressing sleep apnea, a condition where the person’s breathing is interrupted many times throughout the night.Sleep Optimization
  • Supplements – Supplements should be individualized to each person to maximize the benefit. There are multiple botanicals that appear to have anti-inflammatory effects, in some cases supplementation of high quality omega-3 fatty acids is beneficial, and the previously mentioned resolvins also have potential. Since sources of inflammation can vary greatly I recommend seeing a provider, such as a naturopathic physician, who is well-informed about supplement quality, herb-nutrient-drug interactions, and evidence-based use of these formulas.

Support the Lymphatic and Vascular Systems

The lymphatic system is an immune network and waste removal system. When inflammation is present we need our lymphatic system to clear inflammatory debris. In conditions like lymphedema or late stage lipedema with lymphatic involvement, this system isn’t working properly and fluid builds up in tissues, including inflammatory proteins and immune cells like macrophages.

  • Again, eat plenty of phytonutrients – Phytonutrients have a vast array of beneficial actions on the body. Proanthocyanidins are primarily found in berries. These and other compounds can help rebalance connective tissue turnover in venous walls (i.e. matrix metalloproteinases vs. tissue-building enzymes), help reduce inflammation, and even positively affect DNA expression. Proanthocyanidins and tannins have been shown to be beneficial in chronic venous insufficiency and lymphatic insufficiency.(18)
  • Skin Brushing – Skin brushing or dry brushing is a technique that reportedly helps aid lymphatic flow. It is done by using a dry, natural fiber brush and gently brushing your body surface in the direction of lymphatic flow.Exercise
  • Exercise – Both the increase in blood flow and the muscle contractions helping pump lymphatics are 2 of the many benefits exercise can provide for the lymphatic system. Whether it’s walking, swimming, or jumping on a trampoline, being active is vital for vascular and lymphatic health.
  • Other lymphatic and vascular support options like medications and supplements should be personalized to you to address things like cardiovascular disease or lymphedema for example.

Disclaimer: This article is intended only to inform, not to diagnose or treat. Please see your healthcare provider for evaluation of any health concerns.

Continue reading “The Role of Inflammation in Body Weight: An Intro to the Biology of Fat”

How Reducing Toxin Exposure Can Promote a Healthy Weight

It may not surprise you that the majority of my patients come in with some level of concern about their weight. Even if it is not their primary concern, the issue is on their short list. Certainly part of that comes down to societal constructs of what we think we should look like, comparing perfectly healthy bodies to an image that isn’t necessarily right for all. There are, however, many people who are considered overweight or obese and would like to lose weight and these numbers are on the rise.

For most people weight loss is incredibly challenging, even when they do have a healthy lifestyle. Many of these patients wonder if there is something else going on. Why do their bodies respond differently?

There are many nuances to nutrition, nutrient timing, exercise type and intensity that may affect one’s success with body composition goals, but there are also many other factors at play.

Metabolic abnormalities, total cortisol (the stress hormone) and its daily rhythm, the microbiome, genetic differences in how we respond to nutrients, sex hormone imbalances, inflammation, and more can play a part in determining your body weight. Another less commonly discussed factor is toxin exposure.

What is a Toxin?

Hearing the word “toxin” I can’t help but cringe. This term is abused by advertisers that tout products that have vague claims about ridding your body of unnamed toxins without really explaining which toxins they are referring to or how exactly their products work.

I whole-heartedly agree that we are excessively exposed to toxins and that limiting this exposure and supporting our bodies to process them is important, but I’d like to be more specific. In the following paragraphs I hope to put a name to a few of those toxins, inform you of how they can affect body composition, and give you real world examples of what to do about it.

The “Toxins”

There are numerous chemicals potentially involved here, some causing larger problems than others. A large systematic review of studies from 1995-2016 indeed showed a significant positive correlation between pollution exposure and obesity. This study looked at many chemicals, and showed that not all pollutants have the same level of effect on obesity risk, and they influence weight in different ways. Here are a few you should know about:

BPA (and other bisphenols)

One that is associated with higher risk for obesity is BPA. BPA stands for Bisphenol A and is found in plastic water bottles, lining aluminum cans, and even on receipts. Higher urinary BPA levels have been associated with greater risk for abdominal obesity, diabetes, and hypertension. (1) Be careful about trying to bypass this compound by buying “BPA-free” bottles however. There are other bisphenols in plastics that may be just as bad, if not worse, that BPA is replaced with.How Reducing Toxin Exposure Can Promote a Healthy Weight

Phthalates

Phthalates are another component of many plastics that correlate with obesity and insulin resistance. (2) Phthalates are also found in cosmetics, soaps, paint, lubricants, and pesticides. Like many other pollutants, phthalates are known endocrine disruptors. This means they influence hormones like testosterone and estrogen. Phthalates, for example, reduce testosterone contributing to obesity in men. There is even a term for these endocrine disrupting chemicals that cause obesity: obesogens.

Air pollution

Another major consideration is air pollution which can consist of many different chemicals. Several studies, often done in Los Angeles, describe the effects of air pollution on weight and blood sugar control. They found that even ambient air pollution can cause an increased risk of obesity and contribute to insulin resistance, a precursor to type 2 diabetes. (3) (4) (5)

In fact, simply living closer to a major roadway is associated with higher BMI, subcutaneous adipose tissue (fat just under the skin), and visceral adipose tissue (deeper abdominal fat), even when they adjust for lifestyle factors, socioeconomics, demographics, and other factors that could influence these results. (6)How Reducing Toxin Exposure Can Promote a Healthy Weight

POPs

POP stands for Persistent Organic Pollutant, or a pollutant that stays in the environment and builds up over time. POPs are created in some manufacturing processes, industry (including booms like during WWII), agriculture, and more, and are transported around the planet by wind and/or water. Because POPs build up over time they can have significant impacts on human health. For example, the pesticide DDT which was unregistered from use in the United States in 1972, still persists in our environment. Some people believe that exposure to POPs may one day be considered an additional official risk factor for developing type 2 diabetes. (7)

A specific POP, dioxin, has been shown to increase risk for obesity, insulin resistance, and heart disease. (8) Inflammation is one of the primary features of obesity and is one of the mechanisms in which POPs like dioxin increase risk for weight gain as well as associated metabolic conditions. They do this at the genetic level, inducing pro-inflammatory gene expression in fat cells.

We are primarily exposed to POPs in our food, especially meat, because it accumulates in animal tissues.

The Epigenetic Effect

A group at Columbia University studied pregnant women who were exposed to high concentrations of air pollutants and the effects on their children. They found when the mothers were exposed to high levels of these pollutants their children were more than twice as likely to suffer from obesity by the age of seven. This is likely due to a process called epigenetics. (9)How Reducing Toxin Exposure Can Promote a Healthy Weight

Epigenetic changes happen on top of your DNA that essentially turn genes on or off. You inherit your DNA from both of your parents, and you can’t change that, but you can change the way your DNA is expressed through lifestyle factors that affect your epigenome.

One comparison that some people find helpful for understanding this concept is to think of your DNA as your hardware and your epigenome as the software, where the epigenome tells your DNA what to do.

The pollutants the previously mentioned study looked at are known as polycyclic aromatic hydrocarbons (PAHs) which are created when different materials are burned (such as cigarette smoke, forest fires, grilled foods, and car exhaust). How could these products of burning result in obesity? There are likely multiple mechanisms. Alteration in the epigenome is certainly one way, but also via estrogenic activity of PAHs, and by causing fat to accumulate by blocking the breakdown of fats in the body.

The good news is the process of epigenetics can also have your back. It is the reason why your DNA is not your destiny.  Epigenetic changes are not only caused by harmful things like pollution, but can be positively influenced by lifestyle factors like a healthy diet, regular exercise, and avoiding pollutants.

Where Are We Exposed to Chemicals & Pollutants?

We’ve answered this throughout, so you know the short answer is “everywhere.” There are chemicals in mattresses, laundry detergents and dryer sheets, plastics, hair products, cosmetics, air pollution, cigarette smoke, preservatives, in our food, our water, and our lawns. You cannot avoid them completely, but you can do a few things to reduce exposure and support your body’s ability to handle them.

Reducing Your ExposureHow Reducing Toxin Exposure Can Promote a Healthy Weight

  • Avoid microwaving in plastic and drinking out of plastic water bottles.
  • Use good air filters in your home, car, and office.
  • Eat organic.
  • Eat cruciferous vegetables. Cruciferous vegetables like broccoli contain a compound called Sulforaphane which has been shown to increase air pollution excretion from the body like benzene by up to 61%! (9)
  • Eat a plant-based diet. 90% of our exposure to Persistent Organic Pollutants like dioxin is through food. POPs  accumulate in animal tissues, increasing our exposure when we eat more meat. If and when you do eat meat, removing the skin from fish and chicken and checking local water advisories if you catch your own fish can help reduce exposure. (10)
  • Keep air-purifying plants around your home and office. NASA did a study that showed that certain plants are effective at reducing airborne benzene, formaldehyde, and tricholorethylene to near zero in 2 hours and is enhanced by carbon filter systems. (11) Check out a compiled, easy-to-use list at Wikipedia here.
  • Check your cosmetics and other personal care products at the Environmental Working Group’s Skin Deep site for potentially harmful chemicals.
  • See www.EWG.org or their Healthy Living app for more resources.

Works Cited

  1. Bisphenol A and the risk of cardiometabolic disorders: a systematic review with meta-analysis of the epidemiological evidence. Rancière, F, et al., et al. 46, s.l. : Environ Health, 2015, Vol. 14.
  2. Phthalates and metabolism: exposure correlates with obesity and diabetes in men. Phillips, Melissa Lee. 6, s.l. : Environ Health Perspect, 2007, Vol. 115, p. A312.
  3. Longitudinal associations between ambient air pollution with insulin sensitivity, beta-cell function, and adiposity in Los Angeles Latino children. Alderete, TL, et al., et al. s.l. : Diabetes, 2017.
  4. Effects of air pollution exposure on glucose metabolism in Los Angeles minority children. Toledo-Corral, CM, et al., et al. s.l. : Pediatr Obes, 2016.
  5. Ambient air pollutants have adverse effects on insulin and glucose homeostasis in Mexican Americans. Chen, Z, et al., et al. 4, s.l. : Diabetes Care, 2016, Vol. 39, pp. 547-54.
  6. Residential proximity to major roadways, fine particulate matter, and adiposity: the framingham heart study. Li, W, et al., et al. 12, s.l. : Obesity (Silver Spring), 2016, Vol. 24.
  7. Study links exposure to environmental pollutants to obesity, diabetes. American Diabetes Association. Alexandria, Virginia : http://www.diabetes.org, 2014.
  8. Abdominal Obesity and Insulin Resistance in People Exposed to Moderate-to-High Levels of Dioxin. Chang, Jung-Wei, et al., et al. 1, s.l. : PLOS ONE, 2016, Vol. 11.
  9. Association of Childhood Obesity With Maternal Exposure to Ambient Air Polycyclic Aromatic Hydrocarbons During Pregnancy. Rundle, Andrew, et al., et al. 11, s.l. : Am J Epidemiol, 2012, Vol. 175, pp. 1163-1172.
  10. Rapid and sustainable detoxification of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. Egner, Patricia, Chen, Jian-Guo and Zarth, Adam. 8, s.l. : Cancer Prev Res (Phila), 2014, Vol. 7, pp. 813-823.
  11. Dioxins. National Institute of Environmental Health Sciences. [Online] June 2012. https://www.niehs.nih.gov/health/materials/dioxins_new_508.pdf.
  12. Interior landscape plants for indoor air pollution abatement. Wolverton, BC, Johnson, Anne and Bounds, Keith. s.l. : National Aeronautics and Space Administration, 1989.

10 Things You Can do to Help Control Healthy DNA Expression

If you have a parent or other family member with a health condition like high cholesterol or cancer you’ve probably considered you may have a genetic predisposition for those conditions. Though this may be true, it doesn’t mean you can’t influence your risk. It’s no secret that diet and exercise can have positive influences on your health and risk for disease, but now we know it is even affecting how your DNA is expressed.

A little DNA refresher…

You inherit your DNA from each of your parents. Your DNA carries the instructions that determine your growth and development, and produces proteins that are necessary for everyday functioning. Genes are basic units of DNA that interact with each other and the environment.

Epigenetics & Why Your DNA Isn’t Your Destiny

Your DNA isn’t necessarily your fate when it comes to health and disease. The way our DNA is expressed depends on certain modifications that determine if the gene is turned on or off. These are called epigenetic modifications which occur “on top of” the DNA, not to the DNA itself. Diet, lifestyle, and environmental factors can influence genetic expression through epigenetic changes. Continue reading “10 Things You Can do to Help Control Healthy DNA Expression”

8 Reasons Your Probiotic Isn’t Working

Probiotics have become enormously popular, expected to reach $42 billion dollars in global sales this year. [1] This is due largely to our rapidly expanding knowledge of our microbiome and the impacts of gut bacteria on aspects of our health ranging from body composition, mood, genetic expression, immune response, and beyond. There is even a growing field of neurogastroenterology studying the bidirectional communication of the brain-gut axis.

Many of the benefits people report from probiotic use have evidence showing they may indeed be beneficial including relief from antibiotic-associated diarrhea in children [2] and other causes of diarrhea such as C. difficile infection, [3] improved bowel movement and consistency, reduced inflammation associated with the intestinal tract, decreased symptoms of allergy and eczema, and aiding immune function to name a few. [4] Sometimes, however, probiotic supplementation fails to meet expectations. Why is that? Continue reading “8 Reasons Your Probiotic Isn’t Working”

Wine & Broccoli with a Side of Chemistry: Demystifying Sulfur-Based Allergies

broccolifractalThis post was originally published on Whole Health Wellness Center’s website.

Sulfa, sulfur, sulfites, and sulfates are often confused for apparent reasons. Each of these also have the potential to cause adverse reactions in certain people. If you’re allergic to sulfa drugs should you be worried about sulfites? Why are sulfites in wine? Are they in all wine? Can you have a reaction to sulfur? What are the differences in reactions to sulfa, sulfur, sulfates, and sulfites? What should you avoid if you do have an allergy? Continue reading “Wine & Broccoli with a Side of Chemistry: Demystifying Sulfur-Based Allergies”

9 People Who Are Changing the World

Want to change the world? Maybe your inspiration will be found in a common thread found in each of the speakers at the 2014 TEDx event at the University of Washington. Among them were a poetry-writing lawyer, a computer programming biologist, and an engineer setting out to tackle global poverty. As one might expect from any TED event, the talks inspired collaboration and creativity, offering new perspectives on some of the largest problems facing our world. One of my favorite things about TED is the cross-pollination of ideas which the speakers in this set truly exemplify. Until these talks are posted online, here’s the inside scoop!

Continue reading “9 People Who Are Changing the World”