Maternal endotoxemia results in obesity and insulin resistance in adult male offspring.

• Events in utero appear to be important factors contributing to the development of somatic disorders at adult age. The aim of this study was to examine whether maternal immune challenge would be followed at adult age by metabolic and endocrine abnormalities in the offspring. Pregnant rats were given injections of either endotoxin (Escherichia coli lipopolysaccharide; 0.79 mg/kg, ip) or vehicle on days 8, 10, and 12 of gestation. Adult male offspring to lipopolysaccharide-exposed dams were heavier than controls (P < 0.05) and showed increased adipose tissue weights (P < 0.05), elevated food intake (P < 0.05), and increased circulating leptin (P < 0.01). The effect of insulin on glucose uptake was reduced, as measured by an euglycemic hyperinsulinemic clamp technique (P < 0.05). Serum levels of 17beta-estradiol and progesterone were elevated (P < 0.01 and P < 0.05, respectively). Baseline levels of corticosterone were normal, but the corticosterone response to stress was attenuated (P < 0.05), and hippocampal glucocorticoid receptor protein was up-regulated (P < 0.05). Female offspring were uninfluenced, except for increased testosterone levels (P < 0.05), increased baseline corticosterone levels (P < 0.05), and enlargement of heart and adrenals (P < 0.05). The results indicate that maternal endotoxemia leads to obesity, insulin resistance, and high serum levels of leptin in the adult male offspring. This study reports a novel animal model of obesity with features of the metabolic syndrome.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Adipose Tissue

Animals

Blood Glucose

analysis

Body Composition

Brain Chemistry

Carrier Proteins

analysis

Corticosterone

secretion

Endotoxemia

complications

Estradiol

blood

Fatty Acids

Nonesterified

blood

Female

Glucose Clamp Technique

Glycerol

blood

Insulin

blood

Insulin Resistance

Leptin

analysis

Male

Obesity

etiology

Organ Size

Pregnancy

Pregnancy Complications

Prenatal Exposure Delayed Effects

Progesterone

blood

RNA

Messenger

analysis

Rats

Rats

Wistar

Receptors

Cell Surface

Receptors

Glucocorticoid

analysis

genetics

Receptors

Leptin

Stress

Physiological

Testosterone

blood

Publikations- och innehållstyp

ref (ämneskategori)

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