Location: Obesity and Metabolism Research Unit
Title: A high calcium diet containing nonfat dry milk reduces weight gain and associated adipose tissue inflammation in diet-induced obese mice when compared to high calcium alone Authors
Submitted to: Nutrition and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 23, 2012
Publication Date: January 23, 2012
Citation: Thomas, A.P., Dunn, T.N., Drayton, J.B., Oort, P.J., Adams, S.H. 2012. A high calcium diet containing nonfat dry milk reduces weight gain and associated adipose tissue inflammation in diet-induced obsed mice when comparated to high calcium alone. Nutrition and Metabolism. 9:3. Interpretive Summary: Diets that include recommended intakes of dairy foods and calcium have been associated with healthy body weight, but the mechanisms that underlie this association have remained controversial. Some evidence from animal models suggests that calcium alone has anti-obesity effects by lowering fat tissue abundance when fed as part of a high fat diet, whereas much of the literature indicates that other dairy components such as specific amino acids that are rich in dairy foods could play a role. In the current study, we addressed these issues by examining metabolic and inflammatory outcomes in mice fed an obesigenic high fat diet with or without high calcium alone or in the context of a dairy matrix (nonfat dry milk, NFDM). Surprisingly, high calcium fed mice ate more and gained significantly more body fat coupled to increased inflammation in the fat tissue. In contrast, high calcium/NFDM fed mice gained much less weight and fat despite a slight increase in food intake, indicating that some aspect of NFDM must have increased metabolic rate. These animals also displayed improved blood sugar control and less inflammation in fat tissue. We conclude that bioactive components of milk (i.e., amino acids, peptides, and/or carbohydrates) can impact physiology to lead to a healthy phenotype. Further studies in animal models and humans are warranted to determine which specific dairy components most contribute to a healthy metabolism.
Technical Abstract: High dietary calcium (Ca) has been reported to have anti-obesity and anti-inflammatory properties. Evidence for these properties of dietary Ca in animal models of polygenic obesity have been confounded by the inclusion of dairy food components (proteins and/or carbohydrates), thus the individual effect of Ca per se could not be deciphered. Furthermore, potential anti-inflammatory actions of these dietary constituents or Ca in vivo could not be dissociated from reductions in body weight and adiposity. Therefore, we characterized adiposity along with associated metabolic and inflammatory phenotypes in diet-induced obese (DIO) mice fed one of three macronutrient matched high fat diets (45% energy) for 12 weeks: control (0.5% Ca, n=29), high-Ca (1.5% Ca, n=30), or high-Ca + nonfat dry milk (NFDM, n=30). A large sample size per treatment group allowed us to leverage the natural variability in obesity development from high fat feeding to evaluate the impact of increased dietary Ca and NFDM on white adipose tissue (WAT) inflammation in a subset (n = 10/group) of body weight-matched mice. Mice fed NFDM had reduced body weight and adiposity compared to both controls and high-Ca mice (P<0.001). Surprisingly, the high-Ca group had increased body weight and adiposity compared to controls (P<0.001). Hyperphagia and increased feed efficiency contributed to enhanced obesity development in high-Ca mice, in contrast to NFDM mice that displayed significantly reduced weight gain despite higher energy intake compared to controls (reduced feed efficiency in NFDM mice; P<0.001). Retroperitoneal WAT inflammatory mRNA abundance reflected differences in adiposity among treatment groups and mRNA markers of macrophages strongly correlated with body weight in all diet treatment groups; thus, most treatment differences in WAT inflammatory mRNA abundance were lost when comparing body weight-matched mice. Putative anti-obesity properties of high-Ca may require dairy food components to manifest, or alternatively, dairy food components rather than high-Ca per se may be responsible for previously observed anti-obesity effects of calcium/dairy protein-based diets in rodent polygenic obesity models. Additionally, anti-inflammatory properties of feeding high-Ca + NFDM are principally due to adiposity reduction in this DIO rodent model.