Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene

Abstract

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.

Outcome predictability of biomarkers of protein-energy wasting and inflammation in moderate and advanced chronic kidney disease

“…Such mechanisms include sarcopenia-related diminished muscle function, alterations in circulating actin, and gelsolin concentrations (4,29); lower muscle oxidative metabolism (30); impaired immune function (31); decreased sequestration of uremic toxins (32); decreased production of antiinflammatory cytokines and adiponectin (33) by lower fat stores; and atrophy of the gut lining, decreased intestinal secretions, and altered gut flora leading to a reduction in gut function and the ability to absorb nutrients (34). Even though it is unclear whether serum albumin, WBC count, or % LYM are causally involved in the chain of events leading to adverse outcomes, or if they are merely disease markers correlating with the truly causal factors, these associations put into perspective the hypothesis that actionable PEW surrogates are some of the strongest death predictors in CKD.…”

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: Preliminary data from year 9 of the follow-up

“…It is crucial to measure the exposure before disease onset, because adipose tissue POP concentrations can be affected by the treatment and/or by physiological changes resulting from the disease (Brauner et al, 2012b;Jandacek et al, 2005). Additionally, the use of adipose tissue concentrations to estimate historical exposure minimizes possible biases related to misclassification of the exposure.…”

Obesity and kidney disease: hidden consequences of the epidemic

“…These include a benefit from the better nutritional status typically seen in obese individuals, and which provides better protein and energy reserves in the face of acute illness, and a higher muscle mass with enhanced antioxidant capacity 63 and lower circulating actin and higher plasma gelsolin levels 71 , which are associated with better outcomes. Other hypothetically beneficial characteristics of obesity include a more stable hemodynamic status with mitigation of stress responses and heightened sympathetic and renin-angiotensin activity 72 ; increased production of adiponectines 73 and soluble tumor necrosis factor alfa receptors 74 by adipose tissue neutralizing the adverse effects of tumor necrosis factor alfa; enhanced binding of circulating endotoxins 75 by the characteristically higher cholesterol levels seen in obesity; and sequestration of uremic toxins by adipose tissue 76 .…”