Metabolism. 2016 Jan;65(1):48-65.
Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota.
- 1Centre for Infectious Diseases and Control, School of BioSciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
- 2Centre for Infectious Diseases and Control, School of BioSciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India. Electronic address: firstname.lastname@example.org.
Obesity is one of the major challenges for public health in 21st century, with 1.9 billion people being considered as overweight and 600 million as obese. There are certain diseases such as type 2 diabetes, hypertension, cardiovascular disease, and several forms of cancer which were found to be associated with obesity. Therefore, understanding the key molecular mechanisms involved in the pathogenesis of obesity could be beneficial for the development of a therapeutic approach. Hormones such as ghrelin, glucagon like peptide 1 (GLP-1) peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK) secreted by an endocrine organ gut, have an intense impact on energy balance and maintenance of homeostasis by inducing satiety and meal termination. Glucose and energy homeostasis are also affected by lipid sensing in which different organs respond in different ways. However, there is one common mechanism i.e. formation of esterified lipids (long chain fatty acyl CoAs) and the activation of protein kinase C δ (PKC δ) involved in all these organs. The possible role of gut microbiota and obesity has been addressed by several researchers in recent years, indicating the possible therapeutic approach toward the management of obesity by the introduction of an external living system such as a probiotic. The proposed mechanism behind this activity is attributed by metabolites produced by gut microbial organisms. Thus, this review summarizes the role of various physiological factors such as gut hormone and lipid sensing involved in various tissues and organ and most important by the role of gut microbiota in weight management.
KEYWORDS: Gut hormone; LCFA; Obesity; PPAR γ; Probiotic
Obesity in very simple terms can be defined as an abnormal or excessive accumulation of fat which may present a serious threat to an individual health. Its association with risk factors for many chronic diseases such as cardiovascular disease, diabetes and cancer make it more vulnerable to the society. In our review we have focussed on many factors such as role of gut hormones, gut microbiota and more important the way different organs such as brain, liver and gut respond towards lipid exposure. We have also discussed the role of beneficial microbes such as probiotics as a possible therapeutic intervention in obesity .
One very interesting epidemiological fact related to obesity, which we should present here is its occurrence, which previously was considered as a rich nation problem, but according to WHO report it has now spread in low and middle income countries particularly in urban settings. In developing countries and emerging economies the rate of increase in childhood overweight and obesity has been more than 30% higher than in developed countries . Similar reports have suggested India to be the third most obese nation of the world . These facts suggest that obesity is no more confined to few countries but has a prominent global effect and has to be tackled seriously.
Obesity has always been termed as a lifestyle disease. The modern sedentary lifestyle and the diet rich in carbohydrate and fat can be a major cause for the disease. However the fundamental cause for obesity is energy imbalance as the difference is caused by energy consumed and energy expended. If we talk about the low and middle income countries lack of supportive policies in certain sectors such as health, food processing, agriculture, urbanization and education can be a major cause of disease.
Cellular and physiological response towards obesity:
The cellular mechanism involved in fat mass accumulation can be broadly divided into two categories either adipogenesis or increase in the size of adipocytes which may be due to lipid storage. The fate of lipid in mature adipocyte has a major influence in obesity. The storage of lipid in a mature adipocyte depends on four distinct processes namely substrate uptake, lipogenesis, lipolysis and lipid export. These factors may act individually or in combination and may affect fat mass accumulation and hence adiposity . This phenomenon can be better understood with the figure provided below.
Fig.1Various means of lipid storage in adipocyte
Gastrointestinal (GI) tract has also a very prominent role in regulation of energy intake and expenditure. The GI tract is the largest endocrine organ secreting about 20 different hormones. These gut hormones secreted by various organs such as stomach, pancreas, small and large intestine have an intense effect on various hunger and satiety centres. These hormones coordinated by central nervous system (CNS) regulate food intake and meal termination, in this way presenting an example of gut brain axis . Thus it becomes important to see the role of various gut hormones and their consequence on energy accumulation and expenditure
Gut Microbiota and obesity:
The gut microflora is the most complex and diverse microbial niche ranging from 1013-1014 microbes with about 1000 different species . These gut flora has a wide metabolic activity associated with it and can be truly termed as a virtual organ within an organ. The major functions associated with these commensals are protective, structural and metabolic functions. The particular major dominant bacteria present in human large intestine belong to the two major phyla the Gram negative Bacteroidetes and the Gram-positive Firmicutes. The other phyla which are present in variable number include Actinobacteria, Proteobacteria and Verrucomicrobia. Recent studies have revealed how the altered gut microbiota or dysbiois may have an impact on energy balance and may cause various metabolic disorders [Fig 2]. The difference has been reported in both obese and lean counterpart. According to the previous studies the difference is in particular with the representation of Bacteroidetes/ Firmicutes. Hence it can be assumed that this particular ratio between two dominant genera has a prominent role in certain metabolic disease including obesity .
Fig 2: Dysbiosis in the gut microbiota may promote obesity via different mechanisms. These may include increased production of Short chain fatty acid (SCFA), increase in gut permeability and increased lipoprotein lipase (LPL) activity along with decreased fatty acid oxidation. These changes will have certain consequences towards increase in body weight and inflammation. However a restored microbiota with the help of prebiotic and probotics will inhibit all the effects of dysbiosis and will also lead to production of certain gut hormones such as Peptide YY (PYY) and Glucagon like peptide-1 (GLP-1). These gut hormones has certain role in body weight management and energy intake.
Potential dietary solution:
Consumer interest is increasing for food and food component that may be helpful in reducing body weight, providing a possible therapeutic application for obesity. Hence food containing prebiotic and probiotic may provide a suitable source to combat this menace. Various preclinical and clinical trials have indicated towards possible therapeutic role of probiotic in regulating body weight. The probiotics have the ability to reverse the dysbiois caused by diets which are high in fat and low in fibres. Thus probiotics along with prebiotics are prominent players in body weight regulation and maintenance of homeostasis.
 Mishra AK, Dubey V, Ghosh AR. Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota. Metabolism 2016; Jan; 65(1):48-65
 WHO. Obesity and overweight: fact sheet World Health Organisation. http://www.who.int/mediacentre/factsheets/fs311/en/; 2015.
 Masoodi M, Kuda O, Rossmeisl M, Flachs P, Kopecky J. Lipid signaling in adipose tissue: connecting inflammation & metabolism. Biochim Biophys Acta 1851;2015:503–18.
 Votruba SB, Jensen MD. Regional fat distribution as a factor in FFA metabolism. Annu Rev Nutr 2007;27:149–63.
 Ghosh AR. Appraisal of microbial evolution to commensalism and pathogenicity in humans. Clin Med Insights Gastroenterol 2013;6:1–12.
About our Laboratory and Research:
Our center is enormously involved in the active research frontier in the field of gut microbiota and their potential application in human diseases for instance colon cancer and obesity.
Prof. Asit Ranjan Ghosh
Sr. Professor and Assist. Director
Center for Infectious Disease and Control
School of BioSciences and Technology
VIT University, Vellore- 632014, TN, India