Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.     

Dietary supplementation with Agaricus blazei murill extract prevents diet‐induced obesity and insulin resistance in rats

Objective:

Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin‐resistance and low‐grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet‐induced obesity in rats.

Design and Methods:

Wistar rats were fed with control diet (CD) or high‐fat diet (HF) and either with or without supplemented ABM for 20 weeks.

Results:

HF diet‐induced body weight gain and increased fat mass compared to CD. In addition HF‐fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF‐fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet‐induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM‐treated rats suggesting a decrease in lipid absorption.

Conclusions:

Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system.     

Loss of mitochondrial protease ClpP protects mice from diet‐induced obesity and insulin resistance

Caseinolytic peptidase P (ClpP) is a mammalian quality control protease that is proposed to play an important role in the initiation of the mitochondrial unfolded protein response (UPR^mt), a retrograde signaling response that helps to maintain mitochondrial protein homeostasis. Mitochondrial dysfunction is associated with the development of metabolic disorders, and to understand the effect of a defective UPR^mt on metabolism, ClpP knockout (ClpP^?/?) mice were analyzed. ClpP^?/? mice fed ad libitum have reduced adiposity and paradoxically improved insulin sensitivity. Absence of ClpP increased whole‐body energy expenditure and markers of mitochondrial biogenesis are selectively up‐regulated in the white adipose tissue (WAT) of ClpP^?/? mice. When challenged with a metabolic stress such as high‐fat diet, despite similar caloric intake, ClpP^?/? mice are protected from diet‐induced obesity, glucose intolerance, insulin resistance, and hepatic steatosis. Our results show that absence of ClpP triggers compensatory responses in mice and suggest that ClpP might be dispensable for mammalian UPR^mt initiation. Thus, we made an unexpected finding that deficiency of ClpP in mice is metabolically beneficial.     

Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet‐induced obesity rats

Obesity and insulin resistance are rapidly expanding public health problems. These disturbances are related to many diseases, including heart pathology. Acting through the Akt/mTOR pathway, insulin has numerous and important physiological functions, such as the induction of growth and survival of many cell types and cardiac hypertrophy. However, obesity and insulin resistance can alter mTOR/p70S6k. Exercise training is known to induce this pathway, but never in the heart of diet‐induced obesity subjects. To evaluate the effect of exercise training on mTOR/p70S6k in the heart of obese Wistar rats, we analyzed the effects of 12 weeks of swimming on obese rats, induced by a high‐fat diet. Exercise training reduced epididymal fat, fasting serum insulin and plasma glucose disappearance. Western blot analyses showed that exercise training increased the ability of insulin to phosphorylate intracellular molecules such as Akt (2.3‐fold) and Foxo1 (1.7‐fold). Moreover, reduced activities and expressions of proteins, induced by the high‐fat diet in rats, such as phospho‐JNK (1.9‐fold), NF‐kB (1.6‐fold) and PTP‐1B (1.5‐fold), were observed. Finally, exercise training increased the activities of the transduction pathways of insulin‐dependent protein synthesis, as shown by increases in Raptor phosphorylation (1.7‐fold), p70S6k phosphorylation (1.9‐fold), and 4E‐BP1 phosphorylation (1.4‐fold) and a reduction in atrogin‐1 expression (2.1‐fold). Results demonstrate a pivotal regulatory role of exercise training on the Akt/mTOR pathway, in turn, promoting protein synthesis and antagonizing protein degradation. J. Cell. Physiol. 226: 666–674, 2011. © 2010 Wiley‐Liss, Inc.     

Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet‐induced obesity

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high‐fat diet‐induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil‐ and macrophage‐based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi‐infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high‐fat diet, toll‐like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow‐derived macrophages from obese, B. burgdorferi‐infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.     

Intestinal Methanobrevibacter smithii but not total bacteria is related to diet‐induced weight gain in rats

It is increasingly understood that gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, influence host metabolism.

Objective:

Therefore, we compared M. smithii colonization and weight gain in a rat model under different dietary conditions.

Design and Methods:

Sprague‐Dawley rats were inoculated with M. smithii or vehicle (N = 10/group), fed normal chow until day 112 postinoculation, high‐fat chow until day 182, then normal chow until day 253. Thereafter, five rats from each group were fed high‐fat and normal chow until euthanasia.

Results:

Both groups exhibited M. smithii colonization, which increased following inoculation only for the first 9 days. Change to high‐fat chow correlated with significant increases in weight (P < 0.00001) and stool M. smithii (P < 0.01) in all rats, with stool M. smithi decreasing on return to normal chow. Rats switched back to high‐fat on day 253 further increased weight (P < 0.001) and stool M. smithii (P = 0.039). Euthanasia revealed all animals had higher M. smithii, but not total bacteria, in the small intestine than in the colon. Rats switched back to high‐fat chow had higher M. smithii levels in the duodenum, ileum, and cecum than those fed normal chow; total bacteria did not differ in any bowel segment. Rats which gained more weight had more bowel segments colonized, and the lowest weight recorded was in a rat on high‐fat chow which had minimal M. smithii colonization.

Conclusions:

We conclude that M. smithii colonization occurs in the small bowel as well as in the colon, and that the level and extent of M. smithii colonization is predictive of degree of weight gain in this animal model.     

High vapor pressure deficit drives salt‐stress‐induced rice yield losses in India

Flooded rice is grown across wide geographic boundaries from as far north as Manchuria and as far south as Uruguay and New South Wales, primarily because of its adaptability across diverse agronomic and climatic conditions. Salt‐stress damage, a common occurrence in delta and coastal rice production zones, could be heightened by the interactions between high temperature and relative humidity (vapor pressure deficit – VPD). Using temporal and spatial observations spanning 107 seasons and 19 rice‐growing locations throughout India with varying electrical conductivity (EC), including coastal saline, inland saline, and alkaline soils, we quantified the proportion of VPD inducing salinity damage in rice. While controlling for time‐invariant factors such as trial locations, rice cultivars, and soil types, our regression analysis indicates that EC has a nonlinear detrimental effect on paddy rice yield. Our estimates suggest these yield reductions become larger at higher VPD. A one standard deviation (SD) increase in EC from its mean value is associated with 1.68% and 4.13% yield reductions at median and maximum observed VPD levels, respectively. Yield reductions increase roughly sixfold when the one SD increase is taken from the 75th percentile of EC. In combination, high EC and VPD generate near catastrophic crop loss as predicted yield approaches zero. If higher VPD levels driven by global warming materialize in conjunction with rising sea levels or salinity incursion in groundwater, this interaction becomes an important and necessary predictor of expected yield losses and global food security.