Aus Tariq Ali

Insulin resistance in the control of body fat distribution: a new hypothesis.

Obesity causes insulin resistance, which is a prime etiological factor for type 2 diabetes, dyslipidemia, and cardiovascular disease. However, insulin resistance may be a normal physiological response to obesity that limits further fat deposition and which only has pathological effects at high levels. The current hypothesis suggests that in obesity the initial deposition of triglycerides occurs in subcutaneous adipose tissue and as this increases in size insulin resistance will rise and limit further subcutaneous lipid accumulation. Triglycerides will then be diverted to the visceral fat depot as well as to ectopic sites. This leads to a substantial rise in insulin resistance and the prevalence of its associated disorders. Evidence supporting this hypothesis includes studies showing that in lean subjects the prime determinant of insulin resistance is BMI, that is, subcutaneous fat whilst in overweight and obese subjects it is waist circumference and visceral adiposity. It has also been shown that the metabolic syndrome suddenly increases in prevalence at high levels of insulin resistance and we suggest that this is due to the diversion of lipids from the subcutaneous to the visceral depot. This system may have functioned in our evolutionary past to limit excessive adiposity by causing lipid deposition to occur at a site that has maximal effects on insulin resistance but involves minimal weight gain.

Factors predisposing to obesity: a review of the literature

Abstract The rising prevalence of obesity is a worldwide problem affecting not only the developed world but also developing nations such as South Africa. Excess body fat deposition is caused by an imbalance between energy intake and energy expenditure and there are many genetic and environmental factors that can influence this balance. The present article will describe these factors and discuss the complex interaction between the environment and the human genome that may underlie the current obesity epidemic.

The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue.

Background: A previous study has demonstrated that alkaline phosphatase (AP) may play a role in the control of intracellular lipid accumulation in the rodent preadipocyte cell line, 3T3-L1. The present study investigated whether AP may have a similar function in preadipocytes isolated from human mammary gland tissue. Methods: Preadipocyte maturation was induced in the presence or absence of the tissue non-specific AP inhibitors levamisole and histidine, and the tissue-specific AP inhibitor PheGlyGly. Cellular AP activity and adipogenesis were both assessed at 0 and 12 days post-induction of differentiation. Results: After differentiation, AP activity increased 5.1±1.3-fold in the absence and 8.9±2.8-fold (P<0.05) in the presence of levamisole. However, adipogenesis increased 1.95±0.11-fold in the absence but only 1.36±0.06-fold (P<0.001) in the presence of levamisole. There was a 4.2±2.2-fold increase in AP activity in the absence and a 0.51±0.46-fold (P<0.05) decrease in the presence of histidine. Adipogenesis increased 2.09±0.35-fold in the absence of histidine but only 1.22±0.30-fold (P<0.05) in the presence of histidine. PheGlyGly had no effects. Fluorescent microscopy showed AP activity was localized to the triglyceride-containing droplets of the cell. Conclusion: This is the first study to show that tissue non-specific AP inhibitors can block adipogenesis in human preadipocytes.

The Relationship Between Anthropometry and Serum Concentrations of Alkaline Phosphatase Isoenzymes, Liver Enzymes, Albumin, and Bilirubin

Alkaline phosphatase (ALP) is present in human preadipocytes. The aim of this study was to determine the relationship between anthropometry and serum levels of ALP isoenzymes, liver enzymes, albumin, and bilirubin. Anthropometric variables; serum total, bone, liver, and intestinal ALP levels; and alanine aminotransferase (ALT), albumin, total protein, total bilirubin, and g-glutamyltransferase serum levels were measured in 100 volunteers. The levels (given as median [interquartile range]) for total (74.0 U/L [30.0 U/L] vs 62.0 U/L [22.0 U/L]; P <.05) and liver ALP (37.3 U/L [14.6 U/L] vs 26.1 U/L [12.0 U/L]; P < .05) were higher in obese than in lean subjects. The levels of the other ALP isoenzymes and blood analytes were not significantly different between these groups. Albumin and ALT were the only blood proteins studied with serum levels that correlated significantly with waist circumference. This present study demonstrates a relationship between abdominal obesity and serum ALT levels and between body mass index and ALP levels. These findings suggest that serum ALP, particularly liver ALP, is derived from adipose and hepatic tissue.

Body fat distribution and insulin resistance

The movement of populations from rural to urban areas is associated with major changes in lifestyle, particularly the increased availability of calorie-dense foods and drinks. Although obesity is associated with social stigma in Western countries, public opinion of obesity and overweight in the Middle East and Africa is different, being associated more with health and wealth. Obesity occurs when energy intake is greater than energy expenditure. The surplus energy will be stored as fat in the adipose tissue. In the last decade there has been a plethora of data relating to the fact that adipose cells are not just a storage depot for excess calories; rather they are metabolically active tissue. Leptin, and more recently a number of additional hormones, growth factors and cytokines,

Health risks associated with obesity

Obesity is defined clinically as a state of increased body weight, more specifically of increased fat tissue mass. It is associated with increased fat cell size and number, and is usually followed by serious health consequences if not controlled.

Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Abstract Background: Alkaline phosphatase (ALP) controls intracellular lipid accumulation in human preadipocytes, but it is not known whether ALP is expressed in all body fat depots, or whether it has a similar role at all sites. Design: Cross-sectional. Setting and subjects: Subjects undergoing breast reduction and abdominal fat biopsies operations at Charlotte Maxeke Johannesburg Academic Hospital. Outcome measures: This study compared intracellular lipid accumulation and ALP activity in the presence and absence of ALP inhibitors in preadipocytes that were obtained from different adipose depots. Abdominal and mammary gland preadipocytes were isolated from women and induced to differentiate in culture. ALP activity and intracellular lipid levels were measured at baseline and after 12 days of differentiation in the presence and absence of the ALP inhibitors, histidine and levamisole. Results: ALP activity was detected in nondifferentiated abdominal (134 ± 7.5 mU/mg protein) and mammary gland (136 ± 9.6 mU/mg protein) preadipocytes. Its activity had increased significantly (p-value < 0.0005 for both) by day 12 of differentiation (388 ± 55 for abdominal and 278 ± 28 mU/mg protein for mammary). Preadipocytes treated with histidine had lower fat accumulation (p-value < 0.0005) and ALP activity (p-value < 0.005) than nontreated cells on day 12, while those treated with levamisole had lower fat accumulation (p-value < 0.005), but elevated ALP activity (p-value < 0.05), compared to nontreated cells. Lipid accumulation (p-value < 0.005) and ALP activity (p-value < 0.05) were higher in abdominal than mammary gland preadipocytes by day 12. Conclusion: ALP is involved in the control of intracellular lipid accumulation in human preadipocytes that are isolated from both adipose depots. The ability of levamisole to inhibit this process while activating ALP, suggests that this molecule acts via an ALP-independent pathway, while histidine attenuates both lipid deposition and ALP activity.

Ethnic differences in pre-adipocyte intracellular lipid accumulation and alkaline phosphatase activity

Alkaline phosphatase (ALP) increases lipid accumulation in human pre-adipocytes. This study was performed to assess whether ethnic differences in the prevalence of obesity in African and European females are related to differences in pre-adipocyte lipid accretion and ALP activity. Pre-adipocytes were isolated from 13 black and 14 white females. Adipogenesis was quantified using the lipid dye, Oil red O, whilst ALP activity was assayed in cell extracts on day zero and 12days after initiating adipogenesis. Lipid levels (OD units/mg protein) were lower in pre-adipocytes from white than black females on day 0 (0.36±0.05 versus 0.44±0.03, respectively; p<0.0005) and day 12 (1.18±0.14 versus 1.80±0.22, respectively; p<0.0005), as was ALP activity (mU/mg protein) on day zero (36.5±5.8 versus 136.4±10.9, respectively; p<0.0005) and day 12 (127±16 versus 278±27, respectively; p<0.0005). Treatment of pre-adipocytes with histidine, an ALP inhibitor, blocked lipid accumulation. Thus, lipid uptake is higher in pre-adipocytes isolated from black compared to white females which parallels the obesity prevalence rates in these population groups. The reason for higher fat accumulation in pre-adipocytes isolated from black females may be related to higher ALP activity.