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MBPhD Programme

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CHANDARANA, Keval Niranjan

Entered:

2006

Current Position:

Qualified 2011 

PhD title:

The role of gut hormones in bodyweight regulation and glucose homeostasis
 

Principal Supervisor:

Dr Rachel Batterham, Department of Medicine
 

Funding Source:

MRC
 

Description of Project:

Obesity and its associated pathologies are a major cause of morbidity and mortality. It is defined as the excessive accumulation of fat to the extent that health may be impaired. Body weight and energy balance are tightly regulated by a number of homeostatic mechanisms.  The gut hormone peptide YY plays an important role in the regulation of food intake and body weight.  Administration of PYY hormone has been shown to decrease appetite and inhibit food intake in both humans and rodents.  The hormone is released in response to specific macronutrients and in proportion to caloric intake. In addition, exogenous PYY administration to obese human subjects reduces appetite and body weight, raising the possibility of using PYY as a treatment for obesity.  However, little is currently known as to how the gut “senses” the macronutrient composition of food and how the hormones that regulate appetite are released from the gut endocrine cells. PYY is made in the enteroendocrine L-cells which are scattered throughout the gut but represent only 2% of all gut cells. A greater understanding of the mechanisms by which nutrients stimulate the release of such regulatory hormones from the enteroendocrine cells of the gut is essential to the management of obesity.
 

PubMed-accessible Publications:

1. Batterham RL, Kapoor S, Chivers JE, Heffron H, Chandarana K, Herzog H, Le Roux CW, Thomas EL, Bell JD, Withers DJ. Critical role for peptide YY in protein-mediated satiation and body weight regulation. Cell Metabolism 2006 Sep; 4(3):223-33

2. Chandarana K, Batterham R. Peptide YY. Current Opinion in Diabetes, Endocrinology and Obesity. 2008 Feb; 15:65-72

3. Karra E, Chandarana K, Batterham RL. The role of peptide YY in appetite regulation and obesity. Journal of Physiology. 2009 Jan 15; 587(Pt 1):19-25

4. Chandarana K, Drew ME, Emmanuel J, Karra E, Gelegen C, Chan P, Cron NJ, Batterham RL. Subject standardization, acclimatisation and sample processing affect gut hormone levels and appetite in humans. Gastroenterology 2009 Jun;136(7):2115-26

5. Al-Qassab H, Smith MA, Irvine EE, Guillermet-Guibert J, Claret M, Choudhury AI, Selman C, Piipari K, Clements M, Lingard S, Chandarana K, Bell JD, Barsh GS, Smith AJ, Batterham RL, Ashford ML, Vanhaesebroeck B, Withers DJ. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metabolism 2009 Nov;10(5):343-54

6. Chandarana K, Gelegen C, Karra E, Choudhury AI, Drew ME, Fauveau V, Viollet B, Andreelli F, Withers DJ, Batterham RL. Diet and Gastrointestinal Bypass-Induced Weight Loss: The Roles of Ghrelin and Peptide YY. Diabetes 2011 Mar 60; 1-9

7. Chandarana K, Batterham RL. Metabolic insights from cutting the gut. Nature Medicine 2012 May; 18(5):668-669

8. Gelegen C, Chandarana K, Choudhury AI, Al-Qassab H, Evans IM, Irvine EE, Hyde CB, Claret M,  Andreelli F, Sloan SE, Leiter AB, Withers DJ, Batterham RL.Regulation of hindbrain Pyy expression by acute food deprivation, prolonged caloric restriction and weight-loss surgery in mice. American journal of physiology - endocrinology and metabolism. Sep 2012; 303(5):E659-68