Chronic low-dose glucocorticoid treatment increases subcutaneous abdominal fat, but not visceral fat, of male Wistar rats.

AIM: Most studies developed to investigate the effects of glucocorticoids chronic treatment on white adipose tissue uses high doses of these hormones. This study analyzes some effects of a chronic, continuous and steady infusion of low-dose hydrocortisone and the relationship with lipid accumulation in white adipose depots in rats. MAIN METHODS: Nineteen male Wistar rats were divided into control (CON) and cortisol (CORT) groups. Along six weeks CORT group received continuous infusion of 0.6mg/kg/day of hydrocortisone, while CON group received saline. After euthanasia, subcutaneous and visceral (retroperitoneal and mesenteric) fat pads were excised, weighted and analyzed for: lipogenic enzymes activity; molecular changes of 11-hydroxysteroid dehydrogenase type 1 (11ßHSD1) enzyme; enzymes involved in lipid uptake, incorporation, and metabolism and in fatty acids esterification. Besides, morphometric cell analysis was performed. KEY FINDINGS: CORT group showed increased triglycerides, changes in lipoprotein profile and 26,8% increment in central subcutaneous (SC) mass, while visceral fat pads masses remained unchanged. Adipocytes from SC, only, presented increased fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase activity, in addition to reduced AMP-activated protein kinase and 11ßHSD1 enzymes content. SIGNIFICANCE: Chronic low-dose hydrocortisone treatment consequences seem to be different from those commonly seen in long term hypercortisolism. While high doses promote lipid accumulation in visceral depots, a low dose showed an increase in central SC depot only. This appears to involve an increment in lipid storage and in de novo lipogenesis enzymes activity.

Oral ß-hydroxybutyrate increases ketonemia, decreases visceral adipocyte volume and improves serum lipid profile in Wistar rats.

BACKGROUND: Ketosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a ß-hydroxybutyrate (ßHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism. METHODS: ßHB salts were orally administered to provoke elevation in the ketonemia. Effects of this intervention were tested acutely (by gavage) and chronically (4 weeks in drinking water). Acutely, a concomitant glucose overload was used to suppress endogenous ketogenesis and verify whether ßHB salts were really absorbed or not. Long-term administration allowed to weekly evaluate the impact on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat mass, lipid blood profile, serum lipolysis products and adiponectinemia. RESULTS: ßHB salts increased ketonemia in acute and long-term administrations, improved blood lipid profile by raising HDL-cholesterol concentration and decreasing LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated positively with HDLc and negatively with adipocyte volume and serum lipolysis products. CONCLUSIONS: Oral ßHB can rapidly increase ketonemia and, therefore, be used as an acute and long-term animal model of ketosis. Long-term treatment points to important beneficial effects of ketone bodies in serum lipid concentrations and visceral fat mass. These results may help to explain the metabolic adaptations following ketogenic diets, such as a better body fat control and a serum lipid profile improvement.

Atkins diet program rapidly decreases atherogenic index of plasma in trained adapted overweight men.

BACKGROUND: The Atkins diet program is a great example of the application of low carbohydrate diets for obesity, with the intention of weight loss and improvement in cardiovascular risk (CV risk). A good CV risk predictor is the atherogenic index of plasma (AIP) calculated as log (TG/HDL [mmol]), which is strongly affected by serum triglycerides, which in turn is associated with the carbohydrate intake. This study determined the effect of the initial phase of Atkins diet program, consisting in 20 g/day of carbohydrate intake with positive urinary ketones measure, in AIP of 12 adult overweight trained adapted men. The AIP was calculated before and after intervention. RESULTS: After 14 days, BMI and triglycerides decreased significantly, while HDL-C increased. No alterations were described in LDL plasmatic concentration. Prior to the diet, 58.3% of subjects presented high CV risk and after 14 days of the diet program only 33.3% of subjects were classified as high CV risk, while more than 66% were low CV risk. The intervention was effective in 11 of 12 participants. However, in one person the dietary intervention increased AIP index. CONCLUSION: The initial phase of Atkins diet program could significantly decrease the AIP in 11 of 12 adult overweight trained adapted men. Dietary individual responses need to be more studied.

Metabolic adaptations in the adipose tissue that underlie the body fat mass gain in middle-aged rats.

Little is known about adipocyte metabolism during aging process and whether this can influence body fat redistribution and systemic metabolism. To better understand this phenomenon, two animal groups were studied: young-14 weeks old-and middle-aged-16 months old. Periepididymal (PE) and subcutaneous (SC) adipocytes were isolated and tested for their capacities to perform lipolysis and to incorporate D-[U-(14)C]-glucose, D-[U-(14)C]-lactate, and [9,10(n)-(3)H]-oleic acid into lipids. Additionally, the morphometric characteristics of the adipose tissues, glucose tolerance tests, and biochemical determinations (fasting glucose, triglycerides, insulin) in blood were performed. The middle-aged rats showed adipocyte (PE and SC) hypertrophy and glucose intolerance, although there were no significant changes in fasting glycemia and insulin. Furthermore, PE tissue revealed elevated rates (+50 %) of lipolysis during beta-adrenergic-stimulation. There was also an increase (+62 %) in the baseline rate of glucose incorporation into lipids in the PE adipocytes, while these PE cells were almost unresponsive to insulin stimulation and less responsive (a 34 % decrease) in the SC tissue. Also, the capacity of oleic acid esterification was elevated in baseline state and with insulin stimulus in the PE tissue (+90 and 82 %, respectively). Likewise, spontaneous incorporation of lactate into lipids in the PE and SC tissues was higher (+100 and 11 %, respectively) in middle-aged rats. We concluded that adipocyte metabolism of middle-aged animals seems to strongly favor cellular hypertrophy and increased adipose mass, particularly the intra-abdominal PE fat pad. In discussion, we have interpreted all these results as a metabolic adaptations to avoid the spreading of fat that can reach tissues beyond adipose protecting them against ectopic fat accumulation. However, these adaptations may have the potential to lead to future metabolic dysfunctions seen in the senescence.