Increased 11β-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero

Abstract

Nammi S, Dembele K, Nyomba BL. Increased 11␤-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero. Am J Physiol Regul Integr Comp Physiol 292: R1101-R1109, 2007. First published November 22, 2006 doi:10.1152/ajpregu.00255.2006.-Rat offspring prenatally exposed to alcohol display features of metabolic syndrome characterized by a low birth weight, catch-up growth, dyslipidemia, and insulin-resistant diabetes with increased gluconeogenesis, during adult life. Gluconeogenesis is partly regulated by cyclic AMP-and glucocorticoid-dependent mechanisms. Glucocorticoid action at the receptor level depends on its circulating concentrations and is amplified at the prereceptor level by 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1), which regenerates active glucocorticoids from inactive forms. To determine whether 11␤-HSD1 is dysregulated in this rat model, we examined the expression and enzyme activity of 11␤-HSD1 and its regulator enzyme hexose-6-phosphate dehydrogenase (H6PD) in the liver of postnatal day 7 (neonatal) and 3-mo-old (adult) rat offspring prenatally exposed to alcohol. Measurements of 11␤-HSD1 and H6PD were also performed in the omental fat of adult rat offspring. In both neonatal and adult rats, prenatal alcohol exposure resulted in increased tissue corticosterone concentrations, increased expression, and oxoreductase activity of 11␤-HSD1, and a parallel increase of H6PD expression. The data suggest that due to both transcriptional and posttranscriptional dysregulations, rats exposed to alcohol early in life have increased 11␤-HSD1 activity, which may explain insulin-resistant diabetes in these animals later in life. prenatal exposure; programming SEVERAL PRENATAL ADVERSE FACTORS have been implicated in the pathogenesis of chronic diseases in adulthood. The importance of these factors was first recognized by epidemiological studies describing associations between intrauterine growth restriction (IUGR) and insulin resistance, type 2 diabetes, and cardiovascular diseases later in life (6). Since the offspring exposed to such prenatal factors were small at birth, these abnormalities are considered to be a consequence of IUGR. In animal models of IUGR employing malnutrition (44), placental ischemia (53), glucocorticoid exposure (8), or diabetes (62) during pregnancy, the offspring develop insulin resistance, glucose intolerance, and obesity with aging.

Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents

“…Confirming this, a relationship between social stress and visceral fat 11betaHSD1 expression has been found in male mice (Kuo et al, 2007). Moreover, an increase of 11betaHSD1 enzymatic activity has been described in liver and omental adipose tissue as well as in hippocampus of rats prenatally exposed to different stressogenic conditions (Nammi et al, 2007;Wan et al, 2005).…”

Glucose Intolerance in Aging Male IGFBP-3 Transgenic Mice: Differential Effects of Human IGFBP-3 and Its Mutant IGFBP-3 Devoid of IGF Binding Ability

“…Real-time PCR was performed on fat tissue RNA extracts using a protocol described before (9,29). Total RNA, 5 g, was used to synthesize cDNA by reverse transcriptase.…”

Reduction of hepatic glucocorticoid receptor and hexose-6-phosphate dehydrogenase expression ameliorates diet-induced obesity and insulin resistance in mice

“…The microsomal pellet was obtained by centrifugation of the 10 000 g supernatant for 1 h at 100 000 g. Homogenized tissue protein (200 mg) or protein from microsomes (20 mg) was incubated in 100 mM glycine buffer solution (containing 1% BSA (pH 100) and 0 . 5-5 mM glucosamine-6-phosphate (Ropson & Powers 1998, Nammi et al 2007), 1-5 mM NADP) at room temperature for 0-5 min as described (Welberg et al 2000). Specific activities were calculated and expressed as micromoles of NADPH production per minute per milligram of protein.…”

“…0) with 0 . 5 mM NADP as a cofactor (Stegeman & Klotz 1979, Nammi et al 2007. The changes in absorbance at 340 nm were measured over 25 min at 5-min intervals, and the relative H6PDH activity was expressed as above described.…”