Overweight or obesity is usually referred to as more body fat than optimal healthy levels of the body mass index (BMI). A minimum amount of body fat is necessary for a healthy body to support its energy source as well as hormonal, reproductive and immune systems. However, the accumulation of too much fat can impair the body’s movement, flexibility, appearance, and more importantly increase the risk of developing health problems such as heart disease, stroke, and type II diabetes. Overweight or obese adults have increased from more than 1 billion in 2003 to more than 2 billion in 2013.
Being overweight is usually caused by eating too much and moving too little. However, there are other factors that can affect body weight. Among them, the liver and digestive tract health are the most important determining factors. It has been found that patients who are overweight or obese usually also have diseases such as Crohn’s, ulcerative colitis, and NAFLD. In order to address the obesity issue, the GI or liver problem has to be considered as well in addition to a controlled diet and increased exercise.
The GI Lymphatic System and Obesity
70 million people in the United States are affected by digestive diseases every year. GI dysfunction is often a comorbidity with numerous non-intestinal conditions. The GI lymphatic system dysfunction is particularly linked to obesity and metabolic syndrome.
Our lymphatic system is a unidirectional transport system that functions as the 'sewage system' by removing body fluid and metabolic wastes from the cells and returning them to the blood circulation. The lymphatic network consists of blind-ended capillaries located in most tissues that funnel into progressively fewer and larger pre-collecting and collecting vessels. The lymph enters the circulation by passing to the subclavian vein. The lymphatic system is also important in supporting an optimal functioning immune response.
Lymphatics perform essential transport and immune cell regulatory functions to maintain homeostasis in the gastrointestinal (GI) system. Nutrient and fluid absorption in the GI tract requires lymphatic networks to both regulate interstitial fluid balance and transport lipids. GI lymphatics also fulfill important mucosal immune functions in acquired immunity and tolerance because the GI absorptive surface is immense and densely colonized by bacterial commensals.
The lymphatic system in the digestive tract not only collects fluid using collecting lymphatic vessels but also carries, absorbs, and transports dietary lipids using lymphatic capillaries, or lacteals, which are located exclusively in intestinal villi. Although most types of dietary nutrients in the small intestine enter to the blood vessels of the portal venous system to drain into the liver for processing, dietary lipids or fat are passed on to the GI lymphatic capillaries with the exception that small and medium-chain fatty acids are passively diffused to the portal system.
Dilated or restricted lymphatics affects fat absorption and transportation. Animal studies have found that lymphatic defects provoke adult-onset obesity and animals will progress to elevated insulin resistance. Lipid transport by lacteals in the GI is a tightly regulated active process, and the impairment of this regulation could lead to systemic metabolic consequences. The transportation of lipids is through the lymphatic pumping activity which is regulated by intraluminal pressure and wall shear stress. The contraction frequency of intestinal collecting lymphatics will increase following olive oil administration in animal rats. However, when lipid levels are very high they can exert negative effects on lymphatic vessels. As the lipids started rising (within 10–20 minutes) in the mesenteric collecting duct, the vessel responded by reducing contraction frequency and amplitude and constricting the overall vessel diameter. The reduction of the contraction and the vessel diameter is to prevent lipid over absorption. Disruption of this negative regulation mechanism in the lacteals can lead to overload of fat to the body leading to the development of obesity.
Abnormal lymphatic structure and function contribute to adult-onset obesity. This is due to a multifactorial issue involving the gut microbiota as well as the enteric nervous system (ENS). When the lymphatics become dysregulated, this alters the gut bacteria population which further affects the communication of the enteric nervous system (ENS) with the brain and contributes to the accumulation of fat masses. Although the mechanisms of interactions of commensal microbiota and host immunity are still relatively poorly defined, animal studies demonstrated that the absence of commensal microbes is associated with profound intestinal defects of lymphoid tissue architecture and immune functions. This leads to the overpopulation of unfriendly, undesirable, or even pathogenic gut bacteria.
The ENS senses and reacts to the dynamic ecosystem of the GI tract. The ENS communicates to the brain via the brain-gut-axis which includes the vagus nerve and autonomic nervous system (ANS) and signals flow in both directions. The brain-gut axis is involved in many regular functions and systems within our body, including the regulation of eating. When food arrives in the stomach, certain peptide hormones such as cholecystokinin, glucagon-like peptide-1, and peptide YY are secreted. These peptide hormones bind directly and activate receptor targets in the brain and activate signaling pathways from the gut to the brainstem and the hypothalamus to stop food consumption. When we need to take in food before the meal on an empty stomach, the peptide hormone, Ghrelin is released from cells in the gastric mucosa to stimulate the brain to notify the person that they’re hungry and increase food intake. Many undesirable gut bacteria can manufacture the peptide hormone Ghrelin. This leads to increased hunger, as well as cravings for food, sugars, sweeteners and carbohydrates which leads to bloating, poor digestion, and weight gain.
Abnormal lymphatic structure and function not only contribute to adult-onset obesity but also lead to edema, inflammatory injury, and dysregulation of the immune system. If the function of the lymphatics is not working properly, GI functioning and physiology can be greatly affected. The GI immunity can become compromised leading to the overgrowth of pathogenic bacteria and gut inflammation and infection. An altered lymphatic function can cause sluggishness in the waste drainage. Patients will experience body heaviness, fatigue, low energy and easily feel tired. As it progresses to a more severe condition, it can cause many diseases such as Crohn’s, ulcerative colitis, pancreatitis, and Sjogren’s disease. Being overweight is an emerging feature of Crohn's disease. Injury-related gut inflammation can induce an inflammatory lymphatic phenotype and prevents lymphatic regeneration after injury. Another effect of lymphatic insufficiency can be an accumulation of immune cells in the mucosa and submucosa. Prolonged residence of cytotoxic cells within the gut wall is thought to contribute to the immune cell-mediated tissue injury accompanying chronic gut inflammation.
In summary, a lymphatic functional sluggishness in the GI can result in over absorption of fat. A GI lymphatic structural deficiency can cause an absence of commensal microbes and overpopulation of undesirable gut bacteria which produce hormones causing overeating and craving for food and sugar. GI lymphatic functional and structural deficiencies can also cause poor immunity with overgrowth of pathogenic bacteria causing gut inflammation and infections. The resulting waste drainage reduction can cause chronic fatigue and autoimmune conditions.
The Liver and Obesity
The liver is an important organ that plays a central role in the body’s metabolism. In carrying out fat metabolism, one of the key functions includes picking up the long-chain fatty acids from the blood by the liver cells and breaking it down into a series of two carbon acetate units. The liver breaks down many more fatty acids that the hepatocytes need. The extra-large quantities of acetoacetate are exported into the blood. They are then picked up by other tissues to use as the energy source to produce ATPs. Physical and emotional stress can cause decreased blood circulation to the liver through the hepatic artery, resulting in a lack of oxygen to the liver and triggering an increase in reactive oxygen species (ROS). ROS can cause damage to the liver and a decrease in its essential functions. Liver damage and reduced function can cause headaches, nausea, insomnia, mood swings, irritability, blurry vision and hand tremors. Decreased liver function can also reduce the activity of the liver's fatty acid breakdown causing fat accumulation in the liver in the form of triglycerides. The excess triglycerides can also be released into the blood in the form of VLDL. These extra fats will then be deposited into organs such as the heart, kidneys, or stomach. Therefore, weight gain caused by poor liver function is especially apparent around the belly. The fat accumulation in these organs will affect the organ’s performance and people may also experience symptoms of heavy, bloating, fatigue, and sluggishness in addition to the weight gain.
Fat accumulation in the liver also causes many other health conditions. Fatty liver disease is the immediate resulting condition. Excess triglycerides act as a toxin to liver cells and cause liver inflammation leading to NAFLD which can further cause insulin resistance and type II diabetes. Increased VLDL in the blood can cause plaque buildup in the artery walls which narrow the passage and restrict blood flow leading to the development of atherosclerosis. This will increase the risk of heart disease and stroke.
