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Test Tubes

The Effects of Weight Cycling on Health Status and the Gut Microbiome

This paper was written in December, 2018 for a molecular nutrition class.

Weight loss is difficult to achieve and maintain. When weight loss is attempted, one may settle into a repeated cycle of weight loss and regain, often referred to as weight cycling or “yo-yo dieting”. Individuals consistently go “on” diets to lose weight only to find that when they are not on the diet, they gain back the weight lost (and often more than what was originally lost). Weight cycling is not limited to adults in obese body types. It often affects people of normal weights due to societal standards and the common body dissatisfaction brought on by Western culture. The long-term effects of weight cycling not only affect appearance, but also overall health and the gut microbiome on a molecular level.

            Changes to the gut microbiome make long-term weight loss extremely difficult. Obesity affects inflammation as well as gut microbes. When weight is lost, the gut microbiome does not return to its pre-obesity state.1These changes to the composition of the gut microbiome modulate the rate of weight regain.

Despite the numerous studies that prove that dieting is not successful for weight loss long-term, the prevalence of dieting has continuously increased, parallel to the increasing incidence of obesity in the United States over the last 50 years.1The purpose of this paper is to explore the molecular effects of weight cycling on health status including visceral fat accumulation, cardiovascular disease risk and alteration in the composition of tissue lipids. This paper will also examine the effects of yo-yo dieting on the gut microbiome via intestinal flavonoids and the energy balance hormones ghrelin and leptin.


Flavonoids are ingested from the diet and are metabolized by the gut microbiota.4The flavonoids apigenin and naringenin are not recovered in the gut microbiome after weight loss.4These flavonoids play a large role in obesity status. Naringenin prevents obesity and non-shivering thermogenesis by uncoupling protein one (UCP-1) while apigenin inhibits p38 and regulates NAD+levels and acetylation of sirtuin proteins.5Apigenin is used as a treatment for NAD+-dependent metabolic disorders. Obesity depletes these flavonoids and when weight is lost, they are not re-introduced to the gut. This is one of the reasons that weight rebound occurs.5

In the Thaiss, et, the weight cycling mice were treated with apigenin and naringenin to observe the possible mechanisms by which post-dieting obesity is induced. With weight loss, energy expenditure is reduced. Interestingly, the mice administered the flavonoids had normalized energy expenditure levels.4This suggests that apigenin and naringenin may impact energy expenditure. No other metabolic parameters were affected by the flavonoid administration.


On the molecular level, weight loss through repeated diet cycles does not promote health. The molecular effects of weight cycling on health status include visceral fat accumulation, cardiovascular disease risk and alteration in the composition of tissue lipids.1Yo-yo dieting also affects the gut microbiome via intestinal flavonoids apigenin and naringenin. A decrease in apigenin causes a decrease in skeletal muscle while a decrease in naringenin causes glucose intolerance, hepatic steatosis and an increase in muscle triglyceride deposition.6,7Weight cycling also affects the energy balance hormones ghrelin and leptin. On a larger scale, weight cycling increases insulin resistance in type 2 diabetes and promotes dyslipidemia and hypertension.1

Most scientific studies on this topic are extremely recent, so in time, researchers will hopefully complete more studies to get a better understanding of the weight cycling phenomenon on the molecular level. The studies discussed in this paper open up several questions that should be investigated in the future. In order to prevent post-dieting weight gain, researchers must examine what is happening on a molecular level in order to effectively target specific interventions. To impact host energy expenditure and increase the basal metabolic rate, strategies such as prolonged exercise in combination with microbiome-based interventions should be used in future research.3Altering the composition of the intestinal microbiome to observe the effect of post-dieting weight regain should be observed in studies moving forward. One strategy to observe this effect is “post-biotics” in the form of flavonoids.3Because this area of research is new, human studies have yet to be completed (aside from cohort studies). In the future, human studies should be completed. As in the animal studies, the flavonoids apigenin and naringenin should be administered to humans to observe the changes post-diet. Since humans cannot ethically be “sacrificed” for research purposes, observing changes in the human microbiome will be challenging, but data on post-dieting weight regain when administered flavonoids can be obtained. When researchers are able to address the critical importance of the microbiome on post-dieting weight regain, a path toward preventing weight cycling can be created. Once this is established, human studies can be performed, and the puzzle of recurrent obesity may be solved.

This is only an excerpt of my research paper. To read the paper in its entirety, please contact me.


  1. Montani J-P, Viecelli AK, Prévot A, Dulloo AG. Weight cycling during growth and beyond as a risk factor for later cardiovascular diseases: the ‘repeated overshoot’ theory. International Journal of Obesity. 2006;30(S4). doi:10.1038/sj.ijo.0803520.

  2. Karbowska J, Kochan Z, Swierczynski J. Increase of lipogenic enzyme mRNA levels in rat white adipose tissue after multiple cycles of starvation-refeeding. Metabolism. 2001;50(6):734-738. doi:10.1053/meta.2001.23309.

  3. Thaiss CA, Shapiro H, Elinav E. Post-dieting weight gain: the role of persistent microbiome changes. Future Microbiology. 2017;12(7):555-559. doi:10.2217/fmb-2017-0045.

  4. Thaiss CA, Itav S, Rothschild D, et al. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. 2016;540(7634):544-551. doi:10.1038/nature20796.

  5. Chilloux J, Dumas M-E. Are Gut Microbes Responsible for Post-dieting Weight Rebound? Cell Metabolism. 2017;25(1):6-7. doi:10.1016/j.cmet.2016.12.016.

  6. Assini JM, Mulvihill EE, Burke AC, et al. Naringenin Prevents Obesity, Hepatic Steatosis, and Glucose Intolerance in Male Mice Independent of Fibroblast Growth Factor 21. Endocrinology. 2015;156(6):2087-2102. doi:10.1210/en.2014-2003.

  7. Choi WH, Son HJ, Jang YJ, Ahn J, Jung CH, Ha TY. Apigenin Ameliorates the Obesity-Induced Skeletal Muscle Atrophy by Attenuating Mitochondrial Dysfunction in the Muscle of Obese Mice. Molecular Nutrition & Food Research. 2017;61(12):1700218. doi:10.1002/mnfr.201700218.

  8. Venturelli S, Burkard M, Biendl M, Lauer UM, Frank J, Busch C. Prenylated chalcones and flavonoids for the prevention and treatment of cancer. Nutrition. 2016;32(11-12):1171-1178. doi:10.1016/j.nut.2016.03.020.

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