Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background:

Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).

Methods:

In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.

Results:

Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.

Conclusions:

Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.     

New evidence of reproductive organs of <Emphasis Type="Italic">Glossopteris</Emphasis> based on permineralized fossils from Queensland,Australia. I. Ovulate organ <Emphasis Type="Italic">Homevaleia</Emphasis> gen. nov.

This study describes Homevaleia gouldii H. Nishida, Pigg, Kudo et Rigby gen. et sp. nov., an ovule-bearing glossopterid organ, based on a combination of recently collected permineralized specimens from the Late Permian Homevale Station locality in the Bowen Basin of Queensland, Australia, and on previously studied material from the 1977 Gould and Delevoryas study. Homevaleia, which resembles the compression–impression genus Dictyopteridium, is an inrolled megasporophyll with a distinct keel that bears numerous (over 70) stalked ovules on its adaxial surface. Ovules are small, oval, with an elaborate mesh-like structure that is developed from the outermost integumentary layers. Specimens interpreted as representing different developmental stages show there is an apparent interrelationship between megagametophyte development and the opening of the surrounding fertile structure for pollination. Together, new information provided by this material enables better understanding of glossopterid reproductive structure and its function in one distinctive form.     

Paleoactaea gen. nov. (Ranunculaceae) fruits from the Paleogene of North Dakota and the London Clay

Paleoactea nagelii Pigg & DeVore gen. et sp. nov. is described for a small, ovoid ranunculaceous fossil fruit from the Late Paleocene Almont and Beicegel Creek floras of North Dakota, USA. Fruits are 5-7 mm wide, 4.5-6 mm high, 10-13 mm long, and bilaterally symmetrical, containing 10-17 seeds attached on the upper margin in 2-3 rows. A distinctive honeycomb pattern is formed where adjacent seeds with prominent palisade outer cell layers abut. Seeds are flattened, ovoid, and triangular. To the inside of the palisade cells, the seed coat has a region of isodiametric cells that become more tangentially elongate toward the center. The embryo cavity is replaced by an opaline cast. This fruit bears a striking resemblance to extant Actaea, the baneberry (Ranunculaceae), an herbaceous spring wildflower of North Temperate regions. A second species, Paleoactaea bowerbanki (Reid & Chandler) Pigg & DeVore nov. comb., is recognized from the Early Eocene London Clay flora, based on a single fruit. This fruit shares most of the organization and structure of P. nagelii but is larger and has a thicker pericarp. This study documents a rare Paleocene occurrence of a member of the buttercup family, a family that is today primarily herbaceous, and demonstrates a North Atlantic connection for an Actaea-like genus in the Paleogene.     

Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis

Autotaxin (ATX, nucleotide pyrophosphate/phosphodiesterase-2) is an autocrine motility factor initially characterized from A2058 melanoma cell-conditioned medium. ATX is known to contribute to cancer cell survival, growth, and invasion. Recently ATX was shown to be responsible for the lysophospholipase D activity that generates lysophosphatidic acid (LPA). Production of LPA is sufficient to explain the effects of ATX on tumor cells. Cyclic phosphatidic acid (cPA) is a naturally occurring analog of LPA in which the sn-2 hydroxy group forms a 5-membered ring with the sn-3 phosphate. Cellular responses to cPA generally oppose those of LPA despite activation of apparently overlapping receptor populations, suggesting that cPA also activates cellular targets distinct from LPA receptors. cPA has previously been shown to inhibit tumor cell invasion in vitro and cancer cell metastasis in vivo. However, the mechanism governing this effect remains unresolved. Here we show that 3-carba analogs of cPA lack significant agonist activity at LPA receptors yet are potent inhibitors of ATX activity, LPA production, and A2058 melanoma cell invasion in vitro and B16F10 melanoma cell metastasis in vivo.     

Late-summer phytoplankton in western Lake Erie (Laurentian Great Lakes): bloom distributions,toxicity, and environmental influences

Phytoplankton abundance and composition and the cyanotoxin, microcystin, were examined relative to environmental parameters in western Lake Erie during late-summer (2003–2005). Spatially explicit distributions of phytoplankton occurred on an annual basis, with the greatest chlorophyll (Chl) a concentrations occurring in waters impacted by Maumee River inflows and in Sandusky Bay. Chlorophytes, bacillariophytes, and cyanobacteria contributed the majority of phylogenetic-group Chl a basin-wide in 2003, 2004, and 2005, respectively. Water clarity, pH, and specific conductance delineated patterns of group Chl a, signifying that water mass movements and mixing were primary determinants of phytoplankton accumulations and distributions. Water temperature, irradiance, and phosphorus availability delineated patterns of cyanobacterial biovolumes, suggesting that biotic processes (most likely, resource-based competition) controlled cyanobacterial abundance and composition. Intracellular microcystin concentrations corresponded to Microcystis abundance and environmental parameters indicative of conditions coincident with biomass accumulations. It appears that environmental parameters regulate microcystin indirectly, via control of cyanobacterial abundance and distribution.     

Structural, physiological, and stable carbon isotopic evidence that the enigmatic Paleozoic fossil Prototaxites formed from rolled liverwort mats

New structural, nutritional, and stable carbon isotope data may resolve a long-standing mystery-the biological affinities of the fossil Prototaxites, the largest organism on land during the Late Silurian to Late Devonian (420-370 Ma). The tree trunk-shaped specimens, of varying dimensions but consistent tubular anatomy, first formed prior to vascular plant dominance. Hence, Prototaxites has been proposed to represent giant algae, fungi, or lichens, despite incompatible biochemical and anatomical observations. Our comparative analyses instead indicate that Prototaxites formed from partially degraded, wind-, gravity-, or water-rolled mats of mixotrophic liverworts having fungal and cyanobacterial associates, much like the modern liverwort genus Marchantia. We propose that the fossil body is largely derived from abundant, highly degradation-resistant, tubular rhizoids of marchantioid liverworts, intermixed with tubular microbial elements. Our concept explains previously puzzling fossil features and is consistent with evidence for liverworts and microbial associates in Ordovician-Devonian deposits, extensive ancient and modern marchantioid mats, and modern associations of liverworts with cyanobacteria and diverse types of fungi. Our interpretation indicates that liverworts were important components of Devonian ecosystems, that some macrofossils and microfossils previously attributed to "nematophytes" actually represent remains of ancient liverworts, and that mixotrophy and microbial associations were features of early land plants.     

Activation of nuclear factor kappa B in mammary epithelium promotes milk loss during mammary development and infection

We investigated whether nuclear factor kappa B (NF‐κB), which exhibits a regulated pattern of activity during murine mammary gland development, plays an important role during lactation and involution, when milk production ceases and the gland undergoes apoptosis and re‐modeling. We generated a doxycycline inducible transgenic mouse model to activate NF‐κB specifically in the mammary epithelium through expression of a constitutively active form of IKK2, the upstream kinase in the classical NF‐κB signaling cascade. We found that activation of NF‐κB during involution resulted in a more rapid reduction in milk levels and increased cleavage of caspase‐3, an indicator of apoptosis. We also found that activation of NF‐κB during lactation with no additional involution signals had a similar effect. The observation that NF‐κB is a key regulator of milk production led us to investigate the role of NF‐κB during mastitis, an infection of the mammary gland in which milk loss is observed. Mammary gland injection of E. coli LPS resulted in activation of NF‐κB and milk loss during lactation. This milk loss was decreased by selective inhibition of NF‐κB in mammary epithelium. Together, our data reveal that activation of NF‐κB leads to milk clearance in the lactating mammary gland. Therefore, targeting of NF‐κB signaling may prove therapeutic during mastitis in humans and could be beneficial for the dairy industry, where such infections have a major economic impact. J. Cell. Physiol. 222:73–81, 2010. © 2009 Wiley‐Liss, Inc.