IGF-I contributes to glucose homeostasis in the Berlin Fat Mouse Inbred line.

This study aimed to investigate the tissue-specific role of the insulin-like growth factor 1 (IGF-I) on glucose homeostasis in the high-fatness selected Berlin Fat Mouse Inbred (BFMI) line. Therefore, the expression of different IGF-I transcripts and IGF-I protein, IGF-binding proteins, insulin as well as glucose tolerance was analyzed in BFMI in comparison with that in lean mice. In addition, dietary effects were investigated. The BFMI line showed normal blood glucose clearance on standard diet, but on high-fat diet the clearance was impaired, indicating the beginning of insulin resistance. Circulating IGF-I and insulin levels were elevated in BFMI than in lean mice on both diets along with a down-regulation of three IGF-I binding proteins in BFMI mice. Serum IGF-I levels corresponded with the expression pattern for both hepatic and one class II splice variants in reproductive adipose tissue, but not in muscle. High insulin and high IGF-I levels likely prevent BFMI mice from diabetes.

Features of the metabolic syndrome in the Berlin Fat Mouse as a model for human obesity.

BACKGROUND: The Berlin Fat Mouse BFMI860 is a polygenic obesity mouse model which harbors a natural major gene defect resulting in early onset of obesity. To elucidate adult bodily responses in BFMI860 mice that develop juvenile obesity, we studied features of the metabolic syndrome at 20 weeks. METHODS: We examined fat deposition patterns, adipokines, lipid profiles in serum, glucose homeostasis, and insulin sensitivity in mice that were fed either a standard maintenance (SMD) or a high-fat diet (HFD). RESULTS: Like many obese humans, BFMI860 mice showed hyperleptinemia accompanied by hypoadiponectinemia already at SMD that was further unbalanced as a result of HFD. Furthermore, BFMI860 mice had high triglyceride concentrations. However, triglyceride clearance after an oral oil gavage was impaired on SMD but improved on HFD. The oral and intraperitoneal glucose as well as the insulin tolerance tests provided evidence for reduced insulin sensitivity under SMD and insulin resistance on HFD. BFMI860 mice can maintain normal glucose clearance over a wide range of feeding conditions according to an adaptation via increasing the insulin concentrations. CONCLUSIONS: BFMI860 mice show obesity, dyslipidemia, and insulin resistance as three major components of the metabolic syndrome. As these mice develop the described phenotype as a result of a major gene defect, they are a unique model for the investigation of genetic and pathophysiological mechanisms underlying the observed features of the metabolic syndrome and to search for potential strategies to revert the adverse effects under controlled conditions.

High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice.

The aim of this study was to characterize the responses of individual tissues to high-fat feeding as a function of mass, fat composition, and transcript abundance. We examined a panel of eight tissues [5 white adipose tissues (WAT), brown adipose tissue (BAT), liver, muscle] obtained from DBA/2J mice on either a standard breeding diet (SBD) or a high-fat diet (HFD). HFD led to weight gain, decreased insulin sensitivity, and tissue-specific responses, including inflammation, in these mice. The dietary fatty acids were partially metabolized and converted in both liver and fat tissues. Saturated fatty acids (SFA) were converted in the liver to monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), and oleic acid (C18:1) was the preferred MUFA for storage of excess energy in all tissues of HFD-fed mice. Transcriptional changes largely reflected the tissue-specific fat deposition. SFA were negatively correlated with genes in the collagen family and processes involving the extracellular matrix. We propose a novel role of the tryptophan hydroxylase 2 (Tph2) gene in adipose tissues of diet-induced obesity. Tissue-specific responses to HFD were identified. Liver steatosis was evident in HFD-fed mice. Gonadal, retroperitoneal and subcutaneous adipose tissue and BAT exhibited severe inflammatory and immune responses. Mesenteric adipose tissue was the most metabolically active adipose tissue. Gluteal adipose tissue had the highest mass gain but was sluggish in its metabolism. In HFD conditions, BAT functioned largely like WAT in its role as a depot for excess energy, whereas WAT played a role in thermogenesis.

High energy digestion efficiency and altered lipid metabolism contribute to obesity in BFMI mice.

To constitute a valuable resource to identify individual genes involved in the development of obesity, a novel mouse model, the Berlin Fat Mouse Inbred line 860 (BFMI860), was established. In order to characterize energy intake and energy expenditure in obese BFMI860 mice, we performed two independent sets of experiments in male BFMI860 and B6 control mice (10 per line). In experiment 1, we analyzed body fat content noninvasively by dual-energy X-ray absorptiometry and measured resting metabolic rate at thermoneutrality (RMRt) and respiratory quotient (RQ) in week 6, 10, and 18. In a second experiment, energy digested (energy intake minus fecal energy loss) was determined by bomb calorimetry from week 6 through week 12. BFMI860 mice were heavier and had higher fat mass (final body fat content was 24.7% compared with 14.6% in B6). They also showed fatty liver syndrome. High body fat accumulation in BFMI860 mice was restricted to weeks 6-10 and was accompanied by hyperphagia, higher energy digestion, higher RQs, and abnormally high blood triglyceride levels. Lean mass-adjusted RMRt was not altered between lines. These results indicate that in BFMI860 mice, the excessive accumulation of body fat is associated with altered lipid metabolism, high energy intake, and energy digestion. Assuming that BFMI860 mice and their obese phenotypes are of polygenic nature, this line is an excellent model for the study of obesity in humans, especially for juvenile obesity and hyperlipidemia.

Modulation of absorption of beta-carotene and tissue accumulation of beta-carotene and vitamin A by different surfactants in rats.

BACKGROUND/AIMS: The absorption of beta-carotene is closely associated with the absorption of dietary fats in the duodenum. Aim of the study was to evaluate two different surfactants, taurocholate and Pluronic L-81, which are known to stimulate or inhibit the absorption of dietary fats, respectively with regard to the absorption of beta-carotene and tissue accumulation of beta-carotene and vitamin A. METHODS: Rats were kept on a vitamin-A- deficient diet for 4 weeks and then either kept on this diet or fed this diet enriched with beta-carotene (200 mg/kg feed) alone or in combination with taurocholate (10 g/kg) or Pluronic L-81 (5 ml/kg) for another two weeks. RESULTS: beta-carotene was not detectable in liver or plasma of rats fed the deficient diet. The supplementation of beta-carotene alone led to an increase of beta-carotene in plasma and organs (p < 0.05) and resulted in an increase of vitamin A in the liver (p < 0.01), indicating its conversion. The addition of taurocholate enhanced the absorption of beta-carotene (p < 0.01), but had little affect on the levels of total vitamin A in the liver. In contrast, Pluronic L-81 caused a reduced uptake of beta-carotene as indicated by lower concentrations in plasma and liver (p < 0.01) as well as reduced total vitamin A levels in the liver (p < 0.01) either caused by the reduced availability of beta-carotene or a reduced conversion into vitamin A. CONCLUSIONS: The study shows that surfactants can modulate beta-carotene absorption differently. The results for taurocholate confirm known observations concerning an enhanced absorption of beta-carotene. Pluronic L-81 might diminish the uptake of beta-carotene into the enterocyte, which would be in disagreement with regard to its function in the absorption of total lipids in general, or might effect the excretion into the blood by modulation chylomicron secretion.