Today is world obesity day. While we featured already several articles about obesity (Big, Bigger, Obese), dieting (Dieting and the Brain), other ways to loose weight (HCG Injections for Weight Loss) and ideal nutrition (How to Eat Smart), today's article gives a great introduction about the relationship between the brain and the gut and how it is associated with obesity
Obesity - A Burden to Modern Society
Obesity has become one of the major challenges to human health worldwide, most markedly in industrialized countries. In Germany, about half of the adult population is classified as being overweight or obese, with a higher percentage in males (60 %) than in females (44 %) (GEDA, Robert Koch Institute, 2010). Overweight or obese individuals have a high risk of developing comorbidities, including type II diabetes mellitus, hypertension, and coronary heart disease, the most common cause of premature mortality in the obese population.
Body mass stability largely depends on the perfect coupling between caloric intake and energy expenditure [1]. Obesity is a state in which energy intake chronically exceeds energy expenditure. Even a subtle mismatch (less than 0.5 %) in caloric intake over expenditure is sufficient to cause weight gain [2]. The rising prevalence of obesity is likely due to contemporary environmental and lifestyle factors, such as overconsumption of energy-dense food and reduced requirements for physical activity in comparison with the lifestyle of our hunter-gatherer ancestors.
Who is to Blame?
The Brain and the Egg-and-Chicken Principle
The role of the hypothalamus in the regulation of feeding and energy balance was first highlighted by lesion studies in rodents [3, 4]). This brain area comprises specialized neurons that modulate food intake by acting to either stimulate or -suppress appetite (see article by Charlotte Klein). Because of this, the hypothalamus has been determined as a key component in the regulation of metabolic homeostasis "integrating information regarding the body's internal environment and orchestrating a series of coordinated endocrine, autonomic, and behavioral responses that maintain metabolic homeostasis" [5]. However, while great efforts have been made to understand how the brain controls our desire to feed as well as the processes underlying the balancing of energy intake and expenditure, little is known about how the structure and organization of the hypothalamus are altered by obesity. The question still remains whether obesity is a consequence of hypothalamic dysfunction or if it even causes changes in the functionality of the hypothalamus, as has been observed in rodent studies of obesity.
The Role of the Intestinal Tract
Not only the brain, but also the gut takes part in the regulation of appetite and fat storage. There is a long list of factors that originate from the gastrointestinal system and play a role in the management of energy balance by regulating the satiety feeling and thereby, food intake. The main ones are ghrelin, cholecystokinin, peptide YY, pancreatic peptide, glucagon-like peptide 1, and oxyntomodulin (for reviews [6] and [7]).
But these are not the only 'gut factors' controlling energy homeostasis of our organism. Recently, another key player was added to the regulators of our energetic well-being: the intestinal microbiota. These microorganisms, living in our gastrointestinal tract, have coevolved with their human hosts through ages, becoming important for many processes in the human body (see article by Sophie Schweizer). Actually, one could say, we are more microbes than man, because the number of bacterial cells in our intestines exceeds the number of the human cells in our body. Would you believe that the intestinal bacteria have an estimated mass of 1 to 2 kilogram? [9]
It has been shown in studies in mice and humans that the composition and function of microbiota may play a crucial role in the regulation of fat storage and lipid metabolism (more to be read in the article by Jana Foerster). Commensal microorganisms also seem to play a role in some obesity-related comorbidities, for example type II diabetes. Jens Nielsen, at the METAHIT conference in Paris in 2012, even stated that: "Gut microbiota species abundance is a more accurate predictor of type II diabetes than waist-to hip ratio".
Very interesting data have been produced by studies using germ-free mice (animals raised with zero contact to bacteria, see also article by Katarzyna Winek). These mice are leaner than their wild-type littermates, who have about 40 % more fat tissue. After colonization with bacteria from conventionally raised mice, the previously germ-free animals start to gain weight despite decreasing food consumption [10]!
Then, is it the Microbiota Issue?
It is good to take care of our microbial friends: A recently published Nature paper from the group of Martin Blaser describes how subtherapeutic doses of antibiotics can influence the metabolism. They created an adiposity model by introducing antibiotic low-dose treatment. Investigated animals had changes in their microbiome composition and alterations in many metabolic pathways [11]. Another interesting study showed decreased diversity and overall number of gut microbiota in the populations with a high prevalence of severe obesity and its related diseases. Additionally, the most effective obesity treatment (a surgical intervention by gastric banding, sleeve gastrectomy or gastric by-pass, used only in the most severe cases, i.e. BMI ≥ 40) not only leads to improvement in the inflammatory and hormonal status, but also to changes in the gut microbiome. However, up to now only limited data have been produced [12].
Better be Good to Your Commensal Bacteria!
We may say with certainty that we have not yet unraveled all the connections between the gut, the microbiota and the brain or their particular roles in the pathogenesis of obesity, but understanding this signaling in obesity and associated diseases is of huge importance. Recent discoveries and detailed characteristics of pathways involved in the pathogenesis may lead to more effective therapies with multiple targets. It is probably neither the brain nor the gut alone, but a complex interaction of both to blame for round shapes.
[1] Morton et al., Nature, 2006
[2] Hagan and Niswender, Pediatr Blood Cancer, 2012
[3] Tepperman et al., Yale J Biol Med, 1943
[4] Stellar, Psychol Rev, 1954
[5] Williams et al., Eur J Pharmacol, 2011
[6] Small and Bloom, Trends Endocrinol Metab, 2004
[7] Suzuki et al., Exp Diabetes Res, 2012
[8] Murphy and Bloom, Exp Physiol, 2004
[9] Forsythe and Kunze, Cell Mol Life Sci, 2012
[10] Bäckhed et al., Proc Natl Acad sci U S A, 2004
[11] Cho I et al., Nature, 2012
[12] Aron-Widnewsky et al., Nat Rev Gastroenterol Hepatol, 2012
By Charlotte Klein and Katarzyna Winek, PhD Students Medical Neurosciences
Tis article originally appeared December 2012 in Volume 05, Issue 04, Fat Gut or Fat Brain
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