Type-1 transforming growth factor-beta differentially modulates tumoricidal activity of murine peritoneal macrophages against metastatic variants of the B16 murine melanoma.

Transforming growth factor-beta 1 (TGF-beta 1) renders mouse peritoneal macrophages tumoricidal against metastatic variants of the B16 mouse melanoma in vitro. Both direct cytotoxicity and indirect cytotoxicity were observed. A subthreshold concentration (10 U/ml) of recombinant murine interferon-gamma (rMuIFN-gamma) enhanced the direct tumoricidal activity of TGF-beta 1-activated macrophages from 29% to 88% but did not change their indirect tumoricidal profile. Data obtained from macrophages preincubated with either TGF-beta 1 or rMuIFN-gamma showed that TGF-b1 can initiate tumoricidal activity better than rMuIFN-gamma. These effects were plasma-membrane mediated because targeting macrophages with liposomal TGF-beta 1 was ineffective. The order of tumoricidal susceptibility of the B16 melanoma lines to activated macrophages was B16F1 > B16F10 > B16BL6, in inverse order of metastatic potential.

Effects of diets enriched in saturated (palmitic), monounsaturated (oleic), or trans (elaidic) fatty acids on insulin sensitivity and substrate oxidation in healthy adults.

OBJECTIVE: Diets high in total and saturated fat are associated with insulin resistance. This study examined the effects of feeding monounsaturated, saturated, and trans fatty acids on insulin action in healthy adults. RESEARCH DESIGN AND METHODS: A randomized, double-blind, crossover study was conducted comparing three controlled 4-week diets (57% carbohydrate, 28% fat, and 15% protein) enriched with different fatty acids in 25 healthy men and women. The monounsaturated fat diet (M) had 9% of energy as C18:1cis (oleic acid). The saturated fat diet (S) had 9% of energy as palmitic acid, and the trans fatty acid diet (T) had 9% as C18:1trans. Body weight was kept constant throughout the study. After each diet period, insulin pulsatile secretion, insulin sensitivity index (S(I)) by the minimal model method, serum lipids, and fat oxidation by indirect calorimetry were measured. RESULTS: Mean S(I) for the M, S, and T diets was 3.44 +/- 0.26, 3.20 +/- 0.26, and 3.40 +/- 0.26 x 10(-4) min(-1). microU(-1). ml(-1), respectively (NS). S(I) decreased by 24% on the S versus M diet in overweight subjects but was unchanged in lean subjects (NS). Insulin secretion was unaffected by diet, whereas total and HDL cholesterol increased significantly on the S diet. Subjects oxidized the least fat on the M diet (26.0 +/- 1.5 g/day) and the most fat on the T diet (31.4 +/- 1.5 g/day) (P = 0.02). CONCLUSIONS: Dietary fatty acid composition significantly influenced fat oxidation but did not impact insulin sensitivity or secretion in lean individuals. Overweight individuals were more susceptible to developing insulin resistance on high-saturated fat diets.