Chronic Liquid Fructose, but not Glucose, Supplementation Selectively Induces Visceral Adipose Tissue Leptin Resistance and Hypertrophy in Female Sprague‐Dawley Rats

• Published in: Molecular nutrition & food research 2018-11, Vol.62 (22), p.e1800777-n/a
• Main Authors: Sangüesa, Gemma, Roglans, Núria, Montañés, José Carlos, Baena, Miguel, Velázquez, Ana Magdalena, Sánchez, Rosa María, Alegret, Marta, Laguna, Juan Carlos
• Format: Article
• Language: English
• Subjects: Acid resistance; Adiponectin; Adipose tissue; Analytical chemistry; Body weight; Consumption; Eutrophication; Fatty acids; Fructose; Glucose; Homeostasis; Hypertrophy; Hypothalamus; Inflammation; Leptin; Lipolysis; Liver; Markers; Parameters; Phenotypes; Rats; Rodents; Signaling; SOCS3; Sugar; sugar sweetened beverages; Supplements
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201800777

Scope The effect of chronic supplementation with simple‐sugar solutions on leptin signaling in liver, hypothalamus, and visceral white adipose tissue (vWAT) is studied, which is designed to mimic the temporal pattern of consumption by humans. Methods and Results Solutions of fructose or glucose are isocalorically supplemented (7 months) in female Sprague‐Dawley rats consuming ad libitum rodent chow. After sacrifice, plasma and tissue samples (liver, hypothalamus, and vWAT) are collected. Zoometric parameters, plasma analytes, and the tissue expression and activity of markers of leptin signaling are determined by biochemical and molecular biological methods. The two sugars cause different types of adiposopathy. Both sugars induce increases in plasma nonesterified fatty acids, and leptin resistance in the liver and the hypothalamus. Only fructose‐supplemented rats show hyperleptinemia, and increased body weight due to a hypertrophy of vWAT, with no signs of leptin‐mediated lipolysis. Glucose‐supplemented rats show no significant changes in these parameters but present elevated plasma adiponectin concentrations, lipolysis, and inflammatory markers in vWAT, indicating a shift to a nonexpandable adipose tissue phenotype. Conclusion Chronic consumption of fructose places a greater burden on metabolic homeostasis than equivalent consumption of glucose, inducing hyperleptinemia, generalized leptin resistance, and increased body weight due to expanded, hypertrophic vWAT. Adiposopathy is characterized by ectopic fat deposition, increased visceral fat, insulin resistance, adipokine dysregulation and increased inflammatory markers. Liquid fructose and glucose increases plasma NEFA in supplemented rats. Only fructose‐supplemented animals show hyperleptinemia; increased body weight due to a hypertrophy of visceral adipose tissue. Glucose‐supplemented rats show no significant changes in these parameters, present elevated plasma adiponectin, and some inflammatory markers are increased in their vWAT samples, indicating a shift to an unhealthy, un‐expandable adipose tissue phenotype.