Growth hormone ameliorates the impaired glucose tolerance in diet-induced obese mice by regulating visceral fat mass and condition

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 702-709-Obesity: Response to Interventions
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-704
Makoto Fukushima*, Yoshihisa Okamoto, So Ishii, Harumi Katumata, Masaaki Okamoto and Shiro Minami
Nippon Medical School, Kanagawa, Japan
Objective: Growth hormone (GH) is a pituitary hormone with anabolic and lipolytic effects. Adult-growth hormone deficiency patients show visceral fat accumulation with lipid and glucose metabolism similar to metabolic syndrome. On the other hand, obesity with excess visceral fat has been described as a chronic inflammatory and an oxidative stress status closely associated with metabolic syndrome. Recent evidences suggest that adipose dysfunction, e.g. the dysregulation of adipocytokines, reflects the pathophysiologies. In such obese subjects, GH levels are relatively low and its pulsatile secretion is impaired compared with non-obese ones. Thus, GH may control risks for metabolic syndrome by regulating adipose metabolism and function. Here, we investigated the effect of GH on the impaired glucose tolerance, the adipose distribution and function in diet-induced obese (DIO) mice, and that on 3T3-L1 adipocytes under oxidative stress condition.

Methods: Male C57BL/6J mice (12 weeks old) on high fat/high sucrose (HF/HS) diet received bovine GH (5 µg/g body weight) once daily for 6 weeks. Fat distribution (visceral and subcutaneous) was evaluated with X-ray computed tomography (CT) every two weeks and an intra-peritoneal glucose tolerance test (IPGTT) was performed during the last week of experiment. Gene expressions in epididymal white adipose tissue (eWAT) were quantified by real-time RT-PCR. TBARS, a byproduct of lipid peroxidation induced by oxidative stress, in eWAT were measured. 3T3-L1 adipocytes were treated with GH (5-500ng/mL) in the absence or presence of H2O2 (200µM) for 24 hours and the genes including adiponectin (APN) were analyzed by real-time RT-PCR.

Results: No difference in body weight was observed between the two groups of DIO mice (GH and control). However, CT analyses revealed that GH significantly decreased not only visceral fat mass but also subcutaneous one. In accord with these observations, GH treatment decreased the gross weights of eWAT and subcutaneous WAT (sWAT) while increasing those of skeletal muscles. In addition, GH treatment ameliorated the impaired glucose metabolism as assessed by fasting blood glucose, glucose response, and plasma insulin levels in IPGTT. In eWAT, a key adipose tissue in DIO metabolism, the gene expression of APN and IL-10, anti-inflammatory adipocytokines, were raised by GH treatment. Furthermore, TBARS in eWAT were significantly decreased after GH treatment accompanied by the reduced gene expression of glutathione peroxidase, an anti-oxidative enzyme in the same tissue. In the cultured 3T3-L1 adipocytes, addition of GH in media as low as 5 ng/mL enhanced or recovered the lowered gene expression of APN under oxidative stress with H2O2.

Conclusions: GH ameliorates the impaired glucose metabolism in DIO mice by regulating not only adipose mass but also its condition such as inflammation and oxidative stress on visceral fat.

Nothing to Disclose: MF, YO, SI, HK, MO, SM

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