Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor.

OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection. RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance. CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the 'lipotoxicity hypothesis'. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.

Photoalignment of dye-doped cholesteric liquid crystals for electrically tunable patterns with fingerprint textures.

We present a convenient photoalignment approach to fabricate rewritable fingerprint textures with designed geometrical patterns based on methyl red doped cholesteric liquid crystals (MDCLCs). MDCLC systems with/without nanoparticles of polyhedral oligomeric silsesquioxanes (POSS) were employed to realize two types of sophisticated binary patterns, respectively. Based on the understanding of involved mechanisms related to boundary conditions and middle-layer theory, we demonstrated the precise manipulation of fingerprint patterns by varying the fingerprint grating vectors in different domains. Notably, the hybrid-aligned liquid crystal configuration induced by POSS nanoparticles, which leads to the electrically rotatable grating, can be converted into the planar-aligned configuration by the adsorption of photoexcited methyl red molecules onto the indium-tin-oxide (ITO) surface. In this manner, the dynamic voltage-dependent behavior of fingerprint gratings is altered from the rotation mode (R-mode) to the on-off mode (O-mode).

Photoperiod induced obesity in the Brandt's vole (Lasiopodomys brandtii): a model of 'healthy obesity'?

Brandt's voles have an annual cycle of body weight and adiposity. These changes can be induced in the laboratory by manipulation of photoperiod. In the present study, male captive-bred Brandt's voles aged 35 days were acclimated to a short day (SD) photoperiod (8L:16D) for 70 days. A subgroup of individuals (n=16) were implanted with transmitters to monitor physical activity and body temperature. They were then randomly allocated into long day (LD=16L:8D) (n=19, 8 with transmitters) and SD (n=18, 8 with transmitters) groups for an additional 70 days. We monitored aspects of energy balance, glucose and insulin tolerance (GTT and ITT), body composition and organ fat content after exposure to the different photoperiods. LD voles increased in weight for 35 days and then re-established stability at a higher level. At the end of the experiment LD-exposed voles had greater white adipose tissue mass than SD voles (P=0.003). During weight gain they did not differ in their food intake or digestive efficiency; however, daily energy expenditure was significantly reduced in the LD compared with SD animals (ANCOVA, P<0.05) and there was a trend to reduced resting metabolic rate RMR (P=0.075). Physical activity levels were unchanged. Despite different levels of fat storage, the GTT and ITT responses of SD and LD voles were not significantly different, and these traits were not correlated to body fatness. Hence, the photoperiod-induced obesity was independent on disruptions to glucose homeostasis, indicating a potential adaptive decoupling of these states in evolutionary time. Fat content in both the liver and muscle showed no significant difference between LD and SD animals. How voles overcome the common negative aspects of fat storage might make them a useful model for understanding the phenomenon of 'healthy obesity'.

Effects of reproduction on immuno-suppression and oxidative damage, and hence support or otherwise for their roles as mechanisms underpinning life history trade-offs, are tissue and assay dependent.

Life history parameters appear to be traded off against each other, but the physiological mechanisms involved remain unclear. One hypothesis is that potentially energetically costly processes such as immune function and protection from oxidative stress may be compromised during reproductive attempts because of selective resource allocation. Lower temperatures also impose energy costs, and hence allocation decisions might be more pronounced when animals are forced to reproduce in the cold. Here, we experimentally tested whether reproduction at different ambient temperatures was associated with elevated oxidative stress and suppressed immune function in Mongolian gerbils (Meriones unguiculatus). Using a variety of different markers for both immune function and oxidative stress, we found that some measures of immune function (serum bactericidal capacity and size of the thymus) were significantly suppressed, while some measures of oxidative protection [serum superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity] were also reduced, and a marker of oxidative damage (protein carbonyls in serum) was increased in lactating compared with non-reproductive gerbils. These changes were in line with the selective resource allocation predictions. However, the phytohaemagglutinin response and serum total immunoglobulin (IgG) were not suppressed, and other markers of oxidative damage [malondialdehyde (MDA) (TBARS) and protein carbonyls in the liver] were actually lower in lactating compared with non-reproductive gerbils, consistent with increased levels of SOD activity and total antioxidant capacity in the liver. These latter changes were opposite of the expectations based on resource allocation. Furthermore, other measures of protection (GPx levels in the liver and protein thiols in both serum and liver) and damage [MDA (TBARS) in serum] were unrelated to reproductive status. Ambient temperature differences did not impact on these patterns. Collectively, our results indicated that the inferred effects of reproduction on immunosuppression and oxidative damage, and hence support or otherwise for particular physiological mechanisms that underpin life history trade-offs, are critically dependent on the exact markers and tissues used. This may be because during reproduction individuals selectively allocate protection to some key tissues, but sacrifice protection of others.

Ionic Ni(II) complexes containing a triphenylphosphine ligand and an imidazolium cation: synthesis, structures and catalysis for aryl Grignard cross-coupling of aryl halides.

Novel ionic Ni(II) complexes of general formula [R2im][Ni(PPh3)Cl3] (R2im = 1,3-bis(2,6-diisopropylphenyl)imidazolium cation, IPrim, 1a; R2im = 1,3-diisopropylimidazolium cation, (i)Prim, 2a) were easily prepared in high yields by the direct reaction of Ni(PPh3)2Cl2 with 1 equiv. of N,N'-dihydrocarbylimidazolium salt, [R2im]Cl. Their bromide analogs [R2im][Ni(PPh3)Br3] (R2im = IPrim, 1b; R2im = (i)Prim, 2b) were synthesized by the same reaction in the presence of excess NaBr. The reaction of Ni(DME)Cl2 (DME = 1,2-dimethoxyethane) with 2 equiv. of [IPrim]Cl led to the formation of the complex [IPrim]2[NiCl4] (3) in an almost quantitative yield. All these complexes were characterized by elemental analysis, electrospray ionization mass spectrometry (ESI-MS), and (1)H NMR spectroscopy; X-ray crystallography was performed for 1a, 1b, 2a, and 2b. A catalytic study of the cross-coupling reactions of aryl Grignard reagents with aryl halides revealed that complexes 1a and 1b possessed the highest activities. In comparison, complexes 2a, 2b, 3, and the related biscarbene Ni(II) complex Ni(IPr)2Cl2 [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] exhibited moderate activities; the least active complexes were Ni(PPh3)2Cl2 and [NEt4][Ni(PPh3)Cl3].

No evidence for a trade-off between reproductive investment and immunity in a rodent.

Life history theory assumes there are trade-offs between competing functions such as reproduction and immunity. Although well studied in birds, studies of the trade-offs between reproduction and immunity in small mammals are scarce. Here we examined whether reduced immunity is a consequence of reproductive effort in lactating Brandt's voles (Lasiopodomys brandtii). Specifically, we tested the effects of lactation on immune function (Experiment I). The results showed that food intake and resting metabolic rate (RMR) were higher in lactating voles (6≤ litter size ≤8) than that in non-reproductive voles. Contrary to our expectation, lactating voles also had higher levels of serum total Immunoglobulin G (IgG) and anti-keyhole limpet hemocyanin (KLH) IgG and no change in phytohemagglutinin (PHA) response and anti-KLH Immunoglobulin M (IgM) compared with non-reproductive voles, suggesting improved rather than reduced immune function. To further test the effect of differences in reproductive investment on immunity, we compared the responses between natural large (n≥8) and small litter size (n≤6) (Experiment II) and manipulated large (11-13) and small litter size (2-3) (Experiment III). During peak lactation, acquired immunity (PHA response, anti-KLH IgG and anti-KLH IgM) was not significantly different between voles raising large or small litters in both experiments, despite the measured difference in reproductive investment (greater litter size, litter mass, RMR and food intake in the voles raising larger litters). Total IgG was higher in voles with natural large litter size than those with natural small litter size, but decreased in the enlarged litter size group compared with control and reduced group. Our results showed that immune function is not suppressed to compensate the high energy demands during lactation in Brandt's voles and contrasting the situation in birds, is unlikely to be an important aspect mediating the trade-off between reproduction and survival.

Partial removal of brown adipose tissue enhances humoral immunity in warm-acclimated Mongolian gerbils (Meriones unguiculatus).

Temperate rodent species experience marked seasonal fluctuations in environmental temperatures. High thermoregulatory demands during winter usually weaken immune function. Brown adipose tissue (BAT) plays a crucial role in adaptive thermoregulatory process. Thus, we proposed the hypothesis that BAT might participate in the regulation of seasonal changes in immune function. The present study examined the trade-off between thermoregulation and immune function and the potential role of BAT in regulating seasonal changes in immune function in Mongolian gerbils. Specifically, surgical removal of interscapular BAT (34% of total BAT) was performed in male gerbils, and subsequently acclimated to either warm (23 ± 1 °C) or cold (4 ± 1 °C) conditions. Gerbils were then challenged with innocuous antigens and the immune responses were measured. Resting metabolic rate (RMR) and nonshivering thermogenesis (NST) were increased under cold conditions. However, the cost of thermoregulation during cold acclimation did not suppress T-cell mediated immunity and humoral immunity or decrease spleen mass, thymus mass and white blood cells. Partial removal of BAT significantly enhanced humoral immunity in warm-acclimated, but not in cold-acclimated gerbils. T-cell mediated immunity, white blood cells and immune organs were not affected by BAT removal under both warm and cold conditions. Collectively, our results imply that BAT has a suppressive effect on humoral immunity in warm-acclimated gerbils and differential effects of BAT on humoral immunity under different temperatures (e.g., summer and winter) might be benefit to their survival.

Controlled synthesis of nickel(II) dihalides bearing two different or identical N-heterocyclic carbene ligands and the influence of carbene ligands on their structures and catalysis.

Ni(II) dihalides bearing two different or identical NHC ligands have been prepared via a controlled indene elimination synthesis, and the former product provides a new route for the design of biscarbene Ni(II)-based catalysts. The indene elimination reaction of the indenynickel(II) complex (1-H-Ind)Ni(NHC)X (Ind = indenyl) with one equiv. of a distinct imidazolium salt at 100 °C afforded the first example of Ni(II) dihalides bearing two different NHC ligands, i.e., Ni(iPr)(IPr)X(2) [iPr = 1,3-diisopropylimidazol-2-ylidene, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), X = Cl, 1; X = Br, 2] and Ni(iPr)(IMes)Br(2) [IMes = 1,3-bis(mesityl)imidazol-2-ylidene, 3]. Alternatively, complexes 1-3 can be synthesized using a bis-indenyl Ni(II) complex (1-H-Ind)(2)Ni as starting materials via a step-by-step indene elimination at different reaction temperatures. The direct reaction of (1-R-Ind)(2)Ni (R = H or Me) with two equiv. of imidazolium salts at 100 °C afforded Ni(II) dihalides bearing two identical NHC ligands, i.e., Ni(iPr)X(2) (X = Cl, 4; X = Br, 5) and Ni(IPr)Cl(2) (6). All of these complexes were characterized by elemental analysis, NMR spectroscopy and X-ray crystallography for complexes 1-5. The two identical or different NHC ligands in complexes 1-6 changed the coordination sphere of the nickel center from a typical square-planar geometry to a slightly tetrahedral array. A preliminary catalytic study on the cross-coupling reactions of aryl Grignard reagents with aryl halides revealed that complexes 1 and 2 possess the highest activity. In comparison, complexes 3 and 6 exhibited moderate activity and the least active complexes were 4 and 5.