Prenatal Nicotine Exposure Alters Early Pancreatic Islet and Adipose Tissue Development with Consequences on the Control of Body Weight and Glucose Metabolism Later in Life

• Published in: Endocrinology (Philadelphia) Vol. 149; no. 12; pp. 6289 - 6299
• Main Authors: Somm, Emmanuel, Schwitzgebel, Valérie M, Vauthay, Delphine M, Camm, Emily J, Chen, Chang Y, Giacobino, Jean-Paul, Sizonenko, Stéphane V, Aubert, Michel L, Hüppi, Petra S
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01.12.2008
• Subjects: Adipogenesis - drug effects; Adipose Tissue - drug effects; Adipose Tissue - growth & development; Adipose Tissue - metabolism; Animals; Biological and medical sciences; Body Weight - drug effects; Calorimetry; Carbohydrate Metabolism - drug effects; Eating - drug effects; Female; Fundamental and applied biological sciences. Psychology; Ganglionic Stimulants - administration & dosage; Ganglionic Stimulants - toxicity; Glucose - metabolism; Glucose Tolerance Test; Insulin Resistance; Islets of Langerhans - drug effects; Islets of Langerhans - growth & development; Male; Nicotine - administration & dosage; Nicotine - toxicity; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - physiopathology; Rats; Rats, Sprague-Dawley; Vertebrates: endocrinology; Prenatal; Alkaloid; Adipose tissue; Body weight; Langerhans islet; Development; Glucose; Metabolism; Endocrine pancreas; Nicotine
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2008-0361

Despite medical advice, 20–30% of female smokers continue to smoke during pregnancy. Epidemiological studies have associated maternal smoking with increased risk of obesity and type-2 diabetes in the offspring. In the present study, we investigated the impact of prenatal nicotine exposure (3 mg/kg in Sprague Dawley rats via osmotic Alzet minipumps) on the early endocrine pancreas and adipose tissue development in rat pups before weaning. Body weight, fat deposition, food intake and food efficiency, cold tolerance, spontaneous physical activity, glucose utilization, and insulin sensitivity were also examined at adulthood. Prenatal nicotine exposure led to a decrease in endocrine pancreatic islet size and number at 7 d of life (postnatal d 7), which corroborates with a decrease in gene expression of specific transcription factors such as pancreatic and duodenal homeobox 1, Pax-6, Nkx6.1, and of hormones such as insulin and glucagon. The prenatal nicotine exposure also led to an increase in epididymal white adipose tissue weight at weaning (postnatal d 21), and marked hypertrophy of adipocytes, with increased gene expression of proadipogenic transcription factors such as CAAT-enhancer-binding protein-α, peroxisome proliferator activated receptor-γ, and sterol regulatory element binding protein-1C. These early tissue alterations led to significant metabolic consequences, as shown by increased body weight and fat deposition, increased food efficiency on high-fat diet, cold intolerance, reduced physical activity, and glucose intolerance combined with insulin resistance observed at adulthood. These results prove a direct association between fetal nicotine exposure and offspring metabolic syndrome with early signs of dysregulations of adipose tissue and pancreatic development.