Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis, and suppressed secondary bile acid synthesis in the African Americans.

Prolonged calorie restriction increases life span in rodents and other shorter-lived species.¹ Whether this occurs in longer-lived species is unknown, although the effect of prolonged calorie restriction in nonhuman primates is under investigation. One hypothesis to explain the antiaging effects of calorie restriction is reduced energy expenditure with a consequent reduction in the production of reactive oxygen species (ROS).^2,3 However, other metabolic effects associated with calorie restriction, including alterations in insulin sensitivity and signaling, neuroendocrine function, stress response, or a combination of these, may retard aging.⁴

Dysregulation of fatty acid oxidation (FAO) is recognized as important in the pathophysiology of obesity and insulin resistance (IR). However, demonstrating FAO defects in vivo in humans has entailed complex and invasive methodologies. Recently, the identification of genetic blocks in FAO has been vastly simplified by using tandem mass spectrometry (MS/MS) of dried bloodspots to specify acylcarnitine (AcylCN) alterations characteristic for each disorder. This technology has recently been applied to examine FAO alterations in human and animal models of obesity and type 2 diabetes mellitus (T2DM). This study focused on characterizing AcylCN profiles in human plasma from individuals with obesity and T2DM during fasting and insulin‐stimulated conditions. Following an overnight fast, plasma was obtained from lean (n = 12), obese nondiabetic (n = 14), and T2DM (n = 10) participants and analyzed for AcylCN using MS/MS. Plasma samples were also obtained at the end of a 4‐h insulin‐stimulated euglycemic clamp. In obesity and T2DM, long‐chain AcylCNs were similarly significantly increased in the fasted state; free‐CN levels were also elevated. Additionally, T2DM subjects of comparable BMI had increased short‐ and medium‐chain AcylCNs, both saturated and hydroxy, as well as increased C₄‐dicarboxylcarnitine (C₄DC–CN) that correlated with an index of poor glycemic control (HbA_1c; r = 0.74; P < 0.0001). Insulin infusion reduced all species of plasma AcylCN but this reduction was blunted in T2DM. Plasma long‐chain AcylCN species are increased in obesity and T2DM, suggesting that more fatty acids can enter mitochondria. In T2DM, many shorter species accumulate, suggesting that they have a generalized complex oxidation defect.

Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic mic

Background: Dietary fatty acids that are more prone to oxidation than to storage may be less likely to lead to obesity. Objective: The aim of this study was to determine the effect of chain length, degree of unsaturation, and stereoisomeric effects of unsaturation on the oxidation of individual fatty acids in normal-weight men. Design: Fatty acid oxidation was examined in men consuming a weight-maintenance diet containing 40% of energy as fat. After consuming the diet for 1 wk, subjects were fed fatty acids labeled with ¹³C in the methyl or carboxyl position (10 mg/kg body wt). The fatty acids fed in random order were laurate, palmitate, stearate, oleate, elaidate (the trans isomer of oleate), linoleate, and linolenate blended in a hot liquid meal. Breath samples were collected for the next 9 h and the oxidation of each fatty acid was assessed by examining liberated ¹³CO₂ in breath. Results: Cumulative oxidation over the 9-h test ranged from a high of 41% of the dose for laurate to a low of 13% of the dose for stearate. Of the 18-carbon fatty acids, linolenate was the most highly oxidized and linoleate appeared to be somewhat conserved. ¹³C recovery in breath from the methyl-labeled fatty acids was ≈30% less than that from the carboxyl-labeled fatty acids. Conclusions: In summary, lauric acid is highly oxidized, whereas the polyunsaturated and monounsaturated fatty acids are fairly well oxidized. Oxidation of the long-chain, saturated fatty acids decreases with increasing carbon number.

The high and sustained prevalence of obesity is among the most significant public health problems for the 21st century.¹ Rates of severe obesity have increased even faster during the past 3 decades,^2,3 particularly among African American women.¹ This has clinically important implications because of the increased prevalence of comorbid conditions, especially hypertension and type 2 diabetes mellitus,^4,5 among persons with severe obesity.