Polylactose Exhibits Prebiotic Activity and Reduces Adiposity and Nonalcoholic Fatty Liver Disease in Rats Fed a High-Fat Diet

ABSTRACT Background Prebiotic dietary fibers change the intestinal microbiome favorably and provide a health benefit to the host. Objectives Polylactose is a novel fiber, synthesized by extrusion of lactose. We evaluated its prebiotic activity by determining its fermentability, effect on the microbiota, and effects on adiposity and liver lipids in a diet-induced obesity animal model. Methods Male Wistar rats (4–5 wk old) were fed normal-fat (NF, 25% fat energy) or high-fat (HF, 51% fat energy) diets containing different fibers (6% fiber of interest and 3% cellulose, by weight), including cellulose (NFC and HFC, negative and positive controls, respectively), polylactose (HFPL), lactose matched to residual lactose in the HFPL diet, and 2 established prebiotic fibers: polydextrose (HFPD) and fructooligosaccharide (HFFOS). After 10 wk of feeding, organs were harvested and cecal contents collected. Results HFPL animals had greater cecum weight (3 times greater than HFC) and lower cecal pH (∼1 pH unit lower than HFC) than all other groups, suggesting that polylactose is more fermentable than other prebiotic fibers (HFPD, HFFOS; P < 0.05). HFPL animals also had increased taxonomic abundance of the probiotic species Bifidobacterium in the cecum relative to all other groups (P < 0.05). Epididymal fat pad weight was significantly decreased in the HFPL group (29% decrease compared with HFC) compared with all other HF groups (P < 0.05) and did not differ from the NFC group. Liver lipids and cholesterol were reduced in HFPL animals when compared with HFC animals (P < 0.05). Conclusions Polylactose is a fermentable fiber that elicits a beneficial change in the gut microbiota as well as reducing adiposity in rats fed HF diets. These effects of polylactose were greater than those of 2 established prebiotics, fructooligosaccharide and polydextrose, suggesting that polylactose is a potent prebiotic.

Hepatic pyruvate carboxylase expression differed prior to hyperketonemia onset in transition dairy cows

Fatty acids (FA) provide an energy source to the liver during negative energy balance; however, when FA influx is excessive, FA can be stored as liver lipids or incompletely oxidized to β-hydroxybutyrate (BHB). The objectives of this study were to quantify plasma and liver FA profiles and hepatic gene expression in cows diagnosed with hyperketonemia (HYK; BHB ≥ 1.2 mM) or not (nonHYK; BHB < 1.2 mM) to determine a relationship between FA profile and expression of hepatic genes related to oxidation and gluconeogenesis. Production parameters, blood samples (-28, -3, 1, 3, 5, 7, 9, 11, and 14 d relative to parturition; n = 28 cows), and liver biopsies (1, 14, and 28 d postpartum; n = 22 cows) were collected from Holstein cows. Cows were retrospectively grouped as HYK or nonHYK based on BHB concentrations in postpartum blood samples. Average first positive test (BHB ≥ 1.2 mM) was 9 ± 5 d (± SD). Cows diagnosed with HYK had greater C18:1 and lower C18:2 plasma proportions. Liver FA proportions of C16:0 and C18:1 were related to proportions in plasma, but C18:0 and C18:2 were not. Some interactions between plasma FA and HYK on liver FA proportion suggests that there may be preferential use depending upon metabolic state. Cows diagnosed with HYK had decreased pyruvate carboxylase (PC) expression, but no difference at 1 d postpartum in either cytosolic or mitochondrial isoforms of phosphoenolpyruvate carboxykinase (PCK). The increased PC to PCK ratios in nonHYK cows suggests the potential for greater hepatic oxidative capacity, coinciding with decreased circulating BHB. Interestingly, FA, known regulators of PC expression, were not correlated with PC expression at 1 d postpartum. Taken together, these data demonstrate that HYK cows experience a decrease in the ratio of hepatic PC to PCK at 1 day postpartum prior to HYK diagnosis which, on average, manifested a week later. The differential regulation of PC involved in HYK diagnosis may not be completely due to shifts in FA profiles and warrants further investigation.

Role of polar extracts from two quinoa varieties in prevention of steatohepatitis and cardiovascular diseases and improving glucose tolerance in rats.

Introduction: Steatohepatitis, which is the deposition of fat in the liver with inflammation and starting of necrosis, can induce cardiovascular diseases (CVDs). The aim of this research was to study the preventive effects of steatohepatitis and CVD by ethanol extract of two quinoa varieties (quinoa 1 and hualhuas) in rats. Methods: Phenolic and flavonoid compounds were determined in the extracts utilizing colorimetric and high-performance liquid chromatography techniques. The 2,2-diphenyl-1-picryl-hydrazil (DPPH) scavenging activity was assessed for the extracts. Rats were divided into four groups, the first group was fed on a balanced diet (negative control), and other groups consumed a high fructose-fat diet (HFFD) to induce steatohepatitis and CVD. The second group served as a positive control; however, the third and fourth groups were treated by ethanol extract of quinoa 1 and hualhuas, respectively. Different biochemical changes, as well as liver and heart histopathology, were followed. Results: Results showed significant elevation in liver lipids, plasma malondialdehyde, total cholesterol (T-C), triglycerides and low-density lipoprotein cholesterol with reduction of high-density lipoprotein cholesterol (HDL-C) and total antioxidant as well as a significant increase in T-C/HDL-C in control positive group (P < 0.05) compared to control negative group. Plasma parameters and liver lipids were improved by the extracts; hualhuas was superior concerning the effect on lipid while quinoa 1 was more efficient in reducing oxidative stress. The oral glucose tolerance curve and the histopathology of the liver and heart tissues were improved by both extracts. Total phenolic and DPPH scavenging activity were higher in quinoa 1 than hualhuas. Protocatechuic and rutin were the major identified phenolic acid and flavonoid compounds, respectively in the extracts. Conclusion: Quinoa extracts are able to prevent the progression of steatohepatitis and CVD, and might be beneficial in patients with such diseases.

The high-fructose intake of dams during pregnancy and lactation exerts sex-specific effects on adult rat offspring metabolism

Experimental studies have demonstrated the effects of maternal fructose consumption during pregnancy and lactation on metabolic alterations in their offspring, especially male offspring. However, few studies have focused on female offspring after providing fructose in food to dam rats. Here, we studied whether offspring of both sexes were differentially affected by a maternal high-fructose diet (HFD). For this purpose, Sprague-Dawley rats were fed during pregnancy and lactation with a standard diet (SD) or a HFD (50% w/w). After weaning, offspring were fed an SD; 3 days later, dams were sacrificed, and their offspring were sacrificed on postnatal day 90. Body weight (BW), food and water intake (only for dams), and various biomarkers of metabolic syndrome were measured. When compared to the SD-fed dams, HFD-fed dams had a reduction in BW and food and water intake. Conversely, adiposity, liver weight, liver lipids, and plasma levels of glucose, insulin, cholesterol, triglycerides, and uric acid were increased in HFD-fed dams. Moreover, the BW, food consumption, weight of retroperitoneal fat pads, and liver lipids increased in female and male offspring of HFD-fed dams. Interestingly, the pups of HFD-fed mothers showed increased levels of leptin and insulin resistance and decreased levels of adiponectin which were more pronounced in male offspring than in female offspring. In contrast, a higher increase in BW was shown earlier in female offspring. Thus, high-fructose consumption by dams during pregnancy and lactation led to sex-specific developmental programming of the metabolic syndrome phenotype in adult offspring.

Prebiotics Must Achieve a Threshold of Increase in Gut Probiotic Bacteria to Impart Beneficial Health Effects on the Host

Objectives Prebiotic dietary fibers are dietary fibers that] are highly fermented in the large intestine, produce beneficial changes in the gut microbiome, and impart a health benefit to the host. Using reactive extrusion, we have synthesized a novel dietary fiber that is an oligosaccharide of polymerized lactose, which we term polylactose. Here we report on two studies feeding polylactose to rats to determine its prebiotic potential. Methods In Exp. 1, the polylactose preparation contained 51% dietary fiber, 20% free lactose, 5% glucose, and 24% other materials. Rats were fed high fat diets containing 9% total dietary fiber, including cellulose (control, CE, 9%), polylactose (PL, 6%), polydextrose (PD, 6%), and fructooligosaccharide (FOS, 6%). In Exp. 2, the polylactose preparation contained 75% dietary fiber, 9% lactose, 3% glucose, and 13% other materials. Rats were again fed high fat diets containing 9% total dietary fiber, including CE (9%), polylactose (6% or 3%), PD (6%), and galactooligosaccharide (GOS, 6%). In both experiments, rats were fed for 10 weeks, then cecums (empty), cecal contents, livers, and epididymal fat pads were collected. In addition, body composition was determined by MRI. Results In both experiments, final body weight and daily energy intake did not differ among the groups. In Exp. 1, feeding PL greatly increased cecum weight (an indicator of fermentation), cecal Bifidobacterium and Lactobacillus species abundance, increased cecal acetate and propionate, and reduced liver lipids and fat pad weight, compared to the CE group. While PD and FOS increased probiotic species and short chain fatty acids slightly (compared to CE), this was not to the same extent as PL and did not reduce fatty liver and adiposity. In Exp. 2, 6% PL increased cecum weight relative to 3% PF, PD and GOS, all of which were greater than CE. The cecal microbiome was similar among PL (both 3 and 6%), PD, and GOS, all of which differed from CE and were similar to PD and FOS from Exp. 1. Liver lipids, fat pad weight, and body composition did not differ among any of the groups. Conclusions The prebiotic activity of polylactose differed depending on the preparation, for unknown reasons. However, our results suggest there is a threshold of probiotic bacteria abundance that must be attained before beneficial effects are imparted on the host by prebiotics. Funding Sources Midwest Dairy Association.