Amy Noto

Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type 2 diabetes.

Objective: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. Design: Thirty-four participants were randomized into a parallel, controlled trial. Subjects: The participants were adults with type 2 diabetes (age 52.4 ± 1.5 years, body mass index 32.4 ± 1.0 kg/m2, n  =  17 men and 17 women). Interventions: Participants consumed a selection of bakery products containing no flax (control group [CTL], n  =  9), milled flaxseed (FXS, n  =  13; 32 g/d), or flaxseed oil (FXO, n  =  12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). Measures of Outcome: The primary outcome measures were fasting plasma hemoglobin A1c, glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. Results: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. Conclusions: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.

Conjugated linoleic acid reduces hepatic steatosis, improves liver function, and favorably modifies lipid metabolism in obese insulin-resistant rats

CLA has been shown to induce or suppress excess liver lipid accumulation in various animal models. Interestingly, the state of insulin resistance may be an important modulator of this effect. The objective of the current study was to determine how feeding a dietary CLA mixture would affect liver lipid accumulation in insulin-resistant/obese and lean rats in relation to liver function, lipidemia, liver TAG and phospholipid FA composition, and expression of hepatic markers of FA transport, oxidation, and synthesis. Six-week-old fa/fa and lean Zucker rats (n=20/genotype) were fed either a 1.5% CLA mixture or a control diet for 8 wk. CLA supplementation reduced liver lipid concentration of fa/fa rats by 62% in concurrence with improved liver function (lower serum alanine aminotransferase and alkaline phosphatase) and favorable modification of the serum lipoprotein profile (reduced VLDL and LDL and elevated HDL) compared with control-fed fa/fa rats. The fa/fa genotype had two-thirds the amount of CLA (as % total FA) incorporated into liver TAG and phospholipids compared with the lean genotype. In both genotypes, CLA altered the hepatic FA profile (TAG greater than phospholipids) and these changes were explained by a desaturase enzyme index. Liver-FA-binding protein and acyl CoA oxidase, markers of FA transport and oxidation, respectively, were expressed at higher levels in CLA-fed fa/fa rats. In summary, these results illustrate a strong relationship between the state of insulin resistance and liver lipid metabolism and suggest that CLA acts to favorably modify lipid metabolism in fa/fa Zucker rats.

Improved n-3 fatty acid status does not modulate insulin resistance in fa/fa Zucker rats

The objective was to examine the effect of polyunsaturated fatty acid type (plant vs fish oil-derived n-3, compared to n-6 fatty acids in the presence of constant proportions of saturated, monounsaturated and polyunsaturated fatty acids) on obesity, insulin resistance and tissue fatty acid composition in genetically obese rats. Six-week-old fa/fa and lean Zucker rats were fed with a 10% (w/w) mixed fat diet containing predominantly flax-seed, menhaden or safflower oils for 9 weeks. There was no effect of dietary lipid on obesity, oral glucose tolerance (except t=60min insulin), pancreatic function or molecular markers related to insulin, glucose and lipid metabolism, despite increased n-3 fatty acids in muscle and adipose tissue. The menhaden oil diet reduced fasting serum free fatty acids in both fa/fa and lean rats. These data suggest that n-3 composition does not alter obesity and insulin resistance in the fa/fa Zucker rat model when dietary lipid classes are balanced.

Renal metallothionein responds rapidly and site specifically to zinc repletion in growing rats

Metallothionein (MT) is important for heavy metals and free radical protection in the kidney. MT is responsive to zinc and primarily localized within the renal cortex. However, site-specific renal responses to dietary zinc repletion are understudied. The objective of this study was to examine the effects of dietary zinc deficiency and repletion on renal MT concentration and immunolocalization in rats. Weanling male Sprague Dawley rats were randomly assigned to either a zinc-deficient, zinc control, or pair-fed to zinc-deficient group. Half of the zinc-deficient and pair-fed rats were repleted with the control diet ad libitum for an additional 24h. Renal tissue samples were assessed for total zinc, MT concentrations and MT immunostaining. Dietary zinc deficiency reduced renal zinc and MT concentrations, and attenuated intensity and localization of MT. Dietary zinc repletion for 24h restored renal zinc and MT concentrations, the latter primarily in the proximal convoluted tubules of the cortex. Concentrations of renal MT, but not zinc, were elevated by diet restriction and MT (microg/mg protein) and partially normalized by 24h diet repletion. In conclusion, renal MT modification due to zinc deficiency or diet restriction can be rapidly normalized in a site-specific manner with normal dietary zinc intake. The results support a role for MT in kidney homeostasis, in particular at the level of the proximal tubules in the cortex. The speed of MT repletion may have clinical implications for dietary zinc in the treatment of acute and chronic renal pathology due to toxins and free radicals.

Intestinal inflammation in rats induces metallothionein in colonic submucosa.

The aim of the current study was to determine if induction of metallothionein (MT) via acute or chronic dietary zinc supplementation attenuates intestinal inflammation, and to investigate the relationship with site-specific intestinal MT determined by immunolocalization. Growing rats were assigned to zinc-deficient (ZD), acute zinc-treated (ZT), pair-fed, control or chronic Zn-supplemented (ZS) groups. Half the rats in each dietary group received 5% dextran sulphate sodium (DSS) in their drinking water for 4 days. DSS treatment produced acute intestinal inflammation in the colon only, however, dietary zinc deficiency, acute zinc treatment or chronic zinc supplementation did not alter the severity of ulceration. Serum zinc concentrations were attenuated in the DSS-challenged ZT and ZS groups suggesting that zinc was being utilized in some capacity in response to inflammation. DSS-challenge induced MT immunostaining in the colonic submucosa, however, MT was not associated with histological improvements in the present study. The site-specific MT induction in colonic submucosa during intestinal inflammation requires further clarification as a component of the host defense.

Low and High Fat Diets Inconsistently Induce Obesity in C57BL/6J Mice and Obesity Compromises n-3 Fatty Acid Status

C57BL/6J mice are the background strain for multiple models of obesity and diabetes that have genes homologous to those identified in human obesity [1, 2]. C57BL/6J mice are also models of gene-environment induced obesity because they are more susceptible to an environment permissive to obesity and several publications show that high fat (HF) feeding (*40–70% of kcal) induces obesity, insulin resistance, hyperglycemia and leptin resistance [3–9]. We have used this model of high fat feeding to examine interactions of obesity and zinc status but showed neither level of dietary fat nor zinc had an effect on body weight, body mass index, glycemia, insulinemia or leptinemia in C57BL/6J mice [10]. This led to an opportunity to examine whether the inconsistency in development of diet induced obesity (DIO) is related to dietary fat level, or the metabolic derangements associated with greater weight gain. Thus, mice from the original data set [10] were stratified into low body weight (LBW) and high body weight (HBW) groups to determine relationships with metabolic parameters associated with obesity including variations in adipose tissue fatty acid composition and zinc status. The LBW and HBW groups comprised mice fed both low fat (LF) and HF diets, and similar numbers of zinc deficient, control and supplemented mice (Fig. 1). The HBW group displayed greater fasting serum glucose and leptin concentrations (9.8 ± 0.5 vs. 8.2 ± 0.6 mmol/L and 42.6 ± 5.9 vs. 20.3 ± 4.4 ng/ml, respectively; P \ 0.05) compared to the LBW mice. Fasting serum insulin, homeostasis model assessment (HOMA) and zinc were not different between LBW and HBW mice (data not shown). Notably, mice fed a LF diet based on the AIN-93G diet (7 g soybean oil/100 g diet; 16% of calories as fat), were susceptible to obesity, contrary to what others have reported [11–13]. Furthermore, approximately half the mice fed the HF diet were resistant to obesity. The HF diet in our experiment contained a combination of lard and soybean oil (20.9 and 8.8 g/100 g diet, respectively; 55% of calories as fat) to ensure adequate intake of essential fatty acids and this resulted in a HF diet with slightly lower saturated fatty acid content and higher polyunsaturated fatty acid content from linoleic acid compared to protocols in which the high fat diet contains less soybean oil [6, 11]. There are other reports that show HF feeding does not consistently produce obesity in C57BL/6J mice [4, 8].