Suppression of Ghrelin Exacerbates HFCS-Induced Adiposity and Insulin Resistance

Int J Mol Sci. 2017 Jun 19;18(6):1302. doi: 10.3390/ijms18061302.


High fructose corn syrup (HFCS) is widely used as sweetener in processed foods and soft drinks in the United States, largely substituting sucrose (SUC). The orexigenic hormone ghrelin promotes obesity and insulin resistance; ghrelin responds differently to HFCS and SUC ingestion. Here we investigated the roles of ghrelin in HFCS- and SUC-induced adiposity and insulin resistance. To mimic soft drinks, 10-week-old male wild-type (WT) and ghrelin knockout (Ghrelin-/-) mice were subjected to ad lib. regular chow diet supplemented with either water (RD), 8% HFCS (HFCS), or 10% sucrose (SUC). We found that SUC-feeding induced more robust increases in body weight and body fat than HFCS-feeding. Comparing to SUC-fed mice, HFCS-fed mice showed lower body weight but higher circulating glucose and insulin levels. Interestingly, we also found that ghrelin deletion exacerbates HFCS-induced adiposity and inflammation in adipose tissues, as well as whole-body insulin resistance. Our findings suggest that HFCS and SUC have differential effects on lipid metabolism: while sucrose promotes obesogenesis, HFCS primarily enhances inflammation and insulin resistance, and ghrelin confers protective effects for these metabolic dysfunctions.

Keywords: HFCS; adipose tissue inflammation; adiposity; fructose; ghrelin; glucose; insulin resistance; sucrose.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adiposity / drug effects*
  • Animals
  • Blood Glucose / analysis
  • Body Composition
  • Body Weight / drug effects
  • Body Weight / ethnology
  • Diet / adverse effects
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Ghrelin / drug effects*
  • Ghrelin / genetics
  • Ghrelin / metabolism
  • Glucose Tolerance Test
  • High Fructose Corn Syrup / adverse effects*
  • High Fructose Corn Syrup / metabolism
  • Inflammation
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / etiology*
  • Obesity / metabolism
  • Sucrose / adverse effects*
  • Sucrose / metabolism
  • Sweetening Agents / adverse effects


  • Blood Glucose
  • Ghrelin
  • High Fructose Corn Syrup
  • Insulin
  • Sweetening Agents
  • Sucrose