New Insights into Chronic Stress, Obesity, and Metabolic Syndrome: Further Support for an Ecological Model of Health and an Integrated Approach to Care

Ted Schettler MD, MPH
CHE Science Director

Summary

In laboratory animal studies a combination of chronic stress and a high-fat, high-sugar diet causes more abdominal fat to accumulate than that diet alone. This effect seems to be mediated, at least in part, by a substance called Neuropeptide Y (NPY) released from sympathetic nerves supplying adipose tissue in response to certain kinds of stress. A new study reports the same phenomenon in chronically stressed women.[1]

Scientists at UC San Francisco studied a group of 61 disease-free women, about half of whom were chronically stressed caring for a spouse or parent with dementia, while the others were relatively stress-free. They found that the stressed women who ate larger amounts of high-fat, high-sugar food were more prone to abdominal obesity and insulin resistance than the low-stress women who ate the same amount of unhealthy food. As in the animal studies, these effects were also associated with NPY levels, which were significantly higher in the group of stressed women. According to lead author Kirstin Aschbacher, “This study suggests that two women who eat the same thing could have different metabolic responses based on their level of stress. There appears to be a stress pathway that works through diet.”

It’s increasingly clear that chronic stress contributes to obesity, diabetes, and many other disorders. Stress reduction is one of a number of interventions that are likely to help reduce the risk of these diseases and their long-term consequences. Furthermore, these results suggest that epidemiologists should consider whether chronic stress might be influencing associations between dietary habits and various health outcomes when they design studies and analyze data.

Background

The role of acute or chronic stress as a risk factor for various human diseases is generally well recognized although often unaddressed. Headaches, high blood pressure, cardiovascular disease, diabetes, obesity, asthma, depression, anxiety, and cognitive decline are among the disorders in which stress can play an important causal role. Stress reduction can be an important part of an integrated approach to disease prevention or medical care.

Current understanding of the biology of stress comes from decades of animal and human studies. Effects on various hormone levels, neurotransmitters and other signaling compounds, inflammation, gene expression, metabolism, aging, organ development and function, immune responses, and disease progression illustrate the diverse ways in which stress can profoundly influence human health from the sub-cellular to population level, across the life span. One area of current interest is the effect of stress on the risk of developing the metabolic syndrome—a collection of abnormalities including abdominal obesity, insulin resistance, high blood pressure, and abnormal blood lipids.

Metabolic syndrome affects 20-30% of adults worldwide—even more in the US.[2] It is increasingly showing up in disturbing numbers of children and adolescents as well. People with metabolic syndrome have sharply increased risks of cardiovascular disease, type 2 diabetes, cognitive decline, and certain kinds of cancer. Unhealthy diets and lack of exercise are major contributors, but other factors are likely to be involved. For example, in addition to chronic stress, another relatively new area of research is looking at the potential role of environmental chemicals and pollutants.[3] (See also the Diabetes and the Environment website.)

Recently, prospective studies find that chronic stress is predictive of the onset of metabolic syndrome, abdominal fat, and obesity.[4, 5, 6] A meta-analysis concluded that stress reduction can improve blood sugar control in people with type 2 diabetes.[7] Studies in laboratory animals help show how stress can influence insulin sensitivity, weight loss or gain, eating behaviors, and obesity. Cortisol, a well known stress hormone, is only one of many players. Stress-related changes in other hormones and signaling molecules also influence appetite centers in the brain and the cellular response to various kinds of food.

Neuropeptide Y (NPY) is a substance derived from the brain and from sympathetic nerves supplying many different tissues, including fat. In addition to appetite-stimulating effects and regulation of emotional responses, NPY also increases the growth of fat cells and their blood supply. In laboratory mice, some kinds of stress (e.g. exposure to cold water or aggression) cause an increase in NPY levels while others (e.g. restraint stress) do not.[8] Studies in mice also show that chronic stress along with a high-fat, high-sugar diet increases abdominal obesity and a metabolic-like syndrome but only if the stress also causes an increase in NPY levels. More detailed studies showed that nerves in the fat were actually a source of NPY, resulting in accelerated fat accumulation.

Now, scientists at UC San Francisco report similar findings in a group of stressed women.[9] The study participants were 61 disease-free women, about half of whom were chronically stressed caring for a spouse or parent with dementia, while the others were relatively stress-free. The stressed women who ate larger amounts of high-fat, high-sugar food were more prone to abdominal obesity and insulin resistance than the low-stress women who ate the same amount of unhealthy food. And, as in the animal studies, these effects were also associated with NPY levels, which were significantly higher in the group of stressed women. The authors of the study concluded, “There appears to be a stress pathway that works through diet–for example, it could be similar to what we see in animals, where fat cells grow faster in response to junk food when the body is chronically stressed.”

There are some limits to the study. The number of participants was relatively small, and they were post-menopausal, predominantly white women. Whether or not these results apply to younger women and men of various racial or ethnic groups remains to be seen. Nevertheless, finding a stress pathway that works through diet has implications not only for medical care but also for further research.

Until quite recently, studies of the relationships between diet and various diseases have often failed to take into account confounding or effect modification by exercise or physical activity levels.[10] Now it appears that epidemiologists will also need to consider how chronic stress might influence these associations as they design studies and interpret data. For example, in addition to effects on obesity and insulin sensitivity, NPY can stimulate the growth and metastasis of breast cancer and other malignant tumors.[11] It appears increasingly likely that combinations of a high-fat, high-sugar diet and chronic stress will accelerate this response and may also worsen prognosis after the diagnosis and initial treatment of breast cancer.

This new report adds to growing evidence that chronic stress reduction adds value to an integrative approach to prevention and care of diabetes, obesity, cardiovascular disease, and many other common medical and public health concerns. Beyond that these findings should further encourage epidemiologists to use more ecologic models of health and disease as they design studies and interpret data.[12]

 


1. Aschbacher S, Kornfield S, Picard M, et al. Chronic stress increases vulnerability to diet-related abdominal fat, oxidative stress, and metabolic risk. Psychoneuroendocrinology. [Epub before print] http://dx.doi.org/doi:10.1016/j.psyneuen.2014.04.003

2. http://www.reuters.com/article/2010/10/15/us-metabolic-syndrome-idUSTRE69E5FL20101015

3. Thayer K, Heindel J, Bucher J, Gallo M. Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ Health Perspectives. DOI:10.1289/ehp.1104597. Available at http://ehp.niehs.nih.gov/1104597/

4. Pyykkonen A, Raikkonen K, Tuomi T, et al. Stressful life events and the metabolic syndrome: the prevalence, prediction, and prevention of diabetes (PPP)-Botnia Study. Diabetes Care. 2010; 33(2):378-384.

5. Marniemi J, Kronholm E, Aunola S, et al. Visceral fat and psychosocial stress in identical twins discordant for obesity. J Intern Med. 2002; 251(1):35-43.

6. Brunner E, Chandola T, Marmot M. Prospective effect of job strain on general and central obesity in the Whitehall II Study. Am J Epidemol. 2007; 165(7):828-837.

7. Ismail K, Winkley K, Rabe-Hesketh S, et al. Systematic review and meta-analysis of randomized controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes. Lancet. 2004; 363(9421):1589-1597.

8. Kuo L, Kitlinska J, Tilan J, et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med. 2007; 13(7):803-811.

7. Aschbacher S, Kornfield S, Picard M, et al. Chronic stress increases vulnerability to diet-related abdominal fat, oxidative stress, and metabolic risk. Psychoneuroendocrinology. [Epub before print] http://dx.doi.org/doi:10.1016/j.psyneuen.2014.04.003

10. See, for example: Schettler T. The Ecology of Breast Cancer: The Promise of Prevention and the Hope for Healing. Available at: http://sehn.org/new-release-the-ecology-of-breast-cancer-the-promise-of-prevention-and-the-hope-for-healing/

11. Medeiros P, Jackson D. Neuropeptide Y Y5-receptor activation on breast cancer cells acts as a paracrine system that stimulates VEGF expression and secretion to promote angiogenesis. Peptides. 2013; 48:106-113.

12. See The Ecology of Breast Cancer: The Promise of Prevention and the Hope for Healing , chapters 1 and 8, for more detailed discussion of ecological models of health. Available at: http://sehn.org/new-release-the-ecology-of-breast-cancer-the-promise-of-prevention-and-the-hope-for-healing/

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