Obesity: Overview of Weight Management.

INTRODUCTION: Obesity is a chronic illness that requires a multifaceted personalized treatment approach. METHODS & FINDINGS: Using current guidelines and recent studies in weight management, this article reviews the multiple components of weight management: lifestyle intervention (dietary intervention, physical activity, and behavioral interventions), pharmacotherapy, endoscopic procedures, and surgical procedures. This review briefly discusses specific diets and dietary strategies, compensatory mechanisms acting against weight loss, recent changes to Food and Drug Administration approved antiobesity medications, and technological advances in weight management delivery. CONCLUSION: Current literature is lacking large studies on the safety and efficacy of combination therapies involving pharmacotherapy plus 1 or more procedures.

Approach to the Patient: Management of the Post-Bariatric Surgery Patient With Weight Regain.

CONTEXT: Weight regain (WR) after bariatric surgery is emerging as a common clinical problem due to the increase in the number of procedures performed. Early interventions are necessary to curtail the potential recurrence of comorbid conditions. However, it is often difficult to recognize WR early enough to introduce mitigating measures because there are no current guidelines for timely diagnosis and assessment of the severity of this condition. OBJECTIVE: We present a practical approach for the early recognition of WR, based on 11-year follow-up data from our multiethnic bariatric surgery patient population. METHODS: We classify WR according to the rate of increase in weight relative to nadir weight, normalized per 30-day interval. We also review pertinent literature about the etiologic factors contributing to WR after bariatric surgery. RESULTS: According to our algorithm, mild, moderate, and rapid WR are defined as weight increases of 0.2% to <0.5%, 0.5% to 1.0%, and more than 1.0% of nadir weight per 30 days, respectively. Treatment options, including dietary counseling, use of antiobesity medication, and consideration of surgical revision, are described. A case is presented to illustrate the utility of timely identification of WR and the importance of collaboration between bariatric surgeons, obesity medicine specialists, and dietitians. CONCLUSION: Our approach emphasizes the importance of regular long-term follow-up for all bariatric surgery patients.

The Mitigating Effect of Phentermine and Topiramate on Weight Regain After Roux-en-Y Gastric Bypass Surgery.

OBJECTIVE: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon. METHODS: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively. RESULTS: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB. CONCLUSIONS: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.

Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction.

Hyperinsulinemia is strongly associated with type 2 diabetes. Racial and ethnic minority populations are disproportionately affected by diabetes and obesity-related complications. This mini-review provides an overview of the genetic and environmental factors associated with hyperinsulinemia with a focus on racial and ethnic differences and its metabolic consequences. The data used in this narrative review were collected through research in PubMed and reference review of relevant retrieved articles. Insulin secretion and clearance are regulated processes that influence the development and progression of hyperinsulinemia. Environmental, genetic, and dietary factors are associated with hyperinsulinemia. Certain pharmacotherapies for obesity and bariatric surgery are effective at mitigating hyperinsulinemia and are associated with improved metabolic health. Hyperinsulinemia is associated with many environmental and genetic factors that interact with a wide network of hormones. Recent studies have advanced our understanding of the factors affecting insulin secretion and clearance. Further basic and translational work on hyperinsulinemia may allow for earlier and more personalized treatments for obesity and metabolic diseases.

Weight Recidivism After Roux-en-Y Gastric Bypass Surgery: An 11-Year Experience in a Multiethnic Medical Center.

OBJECTIVE: Weight recidivism following Roux-en-Y gastric bypass (RYGB) is common and is associated with recurrence of comorbidities. Studies with long-term follow-up of recidivism quantified by weight regain (WR) are lacking. A retrospective review of all RYGB at our center from 2004 to 2015 was performed to examine the effects of race and type 2 diabetes on WR following RYGB. METHODS: Multivariable linear mixed models were used for the effects of time and race on weight, WR relative to nadir weight (WR/nadir), and WR relative to maximal weight loss, and Cox regressions were used for low, moderate, and high WR/nadir. RESULTS: A total of 1,395 participants were identified. The sample was limited to African American (AA), Caucasian American (CA), and Hispanic American (HA) participants. The effects of time (P < 0.0001), race (P < 0.0001), and race × time interaction (P = 0.0008) on weight trajectory were significant. AA had significantly more WR than CA (P < 0.01). AA and HA had a higher hazard ratio for having low, moderate, and rapid WR/nadir. CONCLUSIONS: Racial disparities after RYGB include WR and particularly affect AA. Understanding the etiologic factors that contribute to these disparities is important to optimize the long-term clinical outcomes of bariatric surgery.

Protein sparing therapies in acute illness and obesity: a review of George Blackburn's contributions to nutrition science.

Protein sparing therapies were developed to mitigate the harms associated with protein-calorie malnutrition and nitrogen losses induced by either acute illness or hypocaloric diets in patients with obesity. We review the development of protein sparing therapies in illness and obesity with a focus on the pioneering contributions of George Blackburn, MD, PhD. He recognized that protein-calorie malnutrition is a common and serious clinical condition and developed new approaches to its treatment in hospitalized patients. His work with stable isotopes and with animal models provided answers about the physiological nutritional requirements and metabolic changes across a spectrum of conditions with varying degrees of stress and catabolism. This led to improvements in enteral and parenteral nutrition for patients with acute illness. Blackburn also demonstrated that lean body mass can be preserved during weight loss with carefully designed very low calorie treatments which became known as the protein sparing modified fast (PSMF). We review the role of the PSMF as part of the comprehensive management of obesity.

ETHNIC AND RACIAL DISPARITIES IN THE BEHAVIORAL, PHARMACOLOGIC, AND SURGICAL TREATMENT OF OBESITY.

Abbreviation: GLP-1 = glucagon-like peptide-1.

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects.

OBJECTIVE: High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. METHODS: Obese subjects (29.0-44.6 kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12 weeks. RESULTS: The age range of subjects was 21-62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2h oral glucose tolerance test did not differ (P>0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet. CONCLUSIONS: Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets.

Fructose consumption and cancer: is there a connection?

PURPOSE OF REVIEW: Cancer cell metabolism is characterized by high rates of glucose uptake and anaerobic glycolysis. Sugar consumption has increased dramatically in the industrialized world, with refined fructose intake skyrocketing upwards in the USA over the past 30 years. Fructose provides an alternative carbon source for glycolysis, entering downstream of glucose and bypassing two key rate-limiting steps. Considering that glycolysis is the major pathway which fuels cancer growth, this review will focus on regulation and flux of glucose versus fructose through this pathway, and consider whether epidemiologic and experimental data support a mechanism whereby fructose might potentiate cancer growth in transformed cells.(Figure is included in full-text article.) RECENT FINDINGS: Fructose intake is associated with increased risk of pancreatic and small intestinal cancers, and possibly others. Fructose promotes flux through the pentose phosphate, which enhances protein synthesis and may indirectly increase tumor growth. Fructose treatment is associated with more aggressive cancer behavior and may promote metastasis. SUMMARY: Whereas glucose favors overall growth kinetics, fructose enhances protein synthesis and appears to promote a more aggressive cancer phenotype. Fructose has become ubiquitous in our food supply, with the highest consumers being teens and young adults. Therefore, understanding the potential health consequences of fructose and its role in chronic disease development is of critical importance.

Preoperative weight gain might increase risk of gastric bypass surgery.

BACKGROUND: Weight loss improves the cardiovascular and metabolic risk associated with obesity. However, insufficient data are available about the health effects of weight gain, separate from the obesity itself. We sought to determine whether the changes in body weight before open gastric bypass surgery (OGB) would have a significant effect on the immediate perioperative hospital course. METHODS: A retrospective chart review of 100 consecutive patients was performed to examine the effects of co-morbidities and body weight changes in the immediate preoperative period on the hospital length of stay and the rate of admission to the surgical intensive care unit (SICU). RESULTS: Of our class III obese patients undergoing OGB, 95% had ≥1 co-morbid condition and an overall SICU admission rate of 18%. Compared with the patients with no perioperative SICU admission, the patients admitted to the SICU had a greater degree of insulin resistance (homeostatic model analysis-insulin resistance 10.8 ± 1.3 versus 5.9 ± 0.5, P = .001), greater serum triglyceride levels (225 ± 47 versus 143 ± 8 mg/dL, P = .003), and had gained more weight preoperatively (.52 ± .13 versus .06 ± .06 lb/wk, P = .003). The multivariate analyses showed that preoperative weight gain was a risk factor for a longer length of stay and more SICU admissions lasting ≥3 days, as were a diagnosis of sleep apnea and an elevated serum triglyceride concentration. CONCLUSION: The results of the present retrospective study suggest that weight gain increases the risk of perioperative SICU admission associated with OGB, independent of the body mass index. Sleep apnea and elevated serum triglyceride levels were also important determinants of perioperative morbidity. In view of the increasing epidemic of obesity and the popularity of bariatric surgical procedures, we propose that additional clinical and metabolic research focusing on the understanding of the complex relationship among obesity, positive energy balance, weight gain, and perioperative morbidity is needed.

Fish oil enhances the antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 on liver cancer cells.

BACKGROUND: Laboratory and epidemiological studies have indicated that 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and dietary omega 3 (omega3)-polyunsaturated fatty acids (PUFAs) are capable of inhibiting the proliferation of various cancer cells. MATERIALS AND METHODS: Human hepatoblastoma cells (HepG2) were treated with 1alpha,25(OH)2D3 and fish oil alone and in combination. Cell proliferation was measured either by the uptake of [3H]-thymidine into DNA or by counting the cell numbers using a hemocytometer. RESULTS: The HepG2 cell proliferation was inhibited by 1alpha,25(OH)2D3 and fish oil in a dose-dependent manner. The lowest effective concentration of 1alpha,25(OH)2D3 was 10(-7) M and 10(-8) M using the [3H]-thymidine incorporation method and the cell counting method, respectively. Fish oil also caused a significant inhibition in HepG2 cell proliferation at 25 microg/mL. When HepG2 cells were treated with 1alpha,25(OH)2D3 in combination with fish oil, it was found that fish oil increased the antiproliferative effect of 1alpha,25(OH)2D3 on HepG2 cell growth compared to treatment with 1alpha,25(OH)2D3 alone. CONCLUSION: 1alpha,25(OH)2D3 could be used to treat hepatocellular carcinoma (HCC). However, the major side-effect of hypercalcemia limits its use. An enhanced 1alpha,25(OH)2D3-induced inhibition of HepG2 cell proliferation in the presence of PUFAs in the form of fish oil suggests that a lower concentration of 1alpha,25(OH)2D3 could be used to treat hepatocellular carcinoma in the presence of PUFAs to decrease the risk of hypercalcemia caused by high concentrations of 1alpha,25(OH)2D3.

Weight loss and health outcomes in African Americans and whites after gastric bypass surgery.

OBJECTIVE: The objective was to describe differences in weight loss, dietary intake, and cardiovascular risk factors between white and African-American patients after gastric bypass (GBP). RESEARCH METHODS AND PROCEDURES: This was a retrospective database review of a sample of 84 adult patients (24 African-American and 60 white women and men) between the ages of 33 and 53 years. All subjects had GBP surgery in 2001 at the Bariatric Surgery Program at Boston Medical Center in Boston, MA, and were followed for one year postoperatively. Patients were excluded if weight data were missing at baseline, 3 months, or 1 year after GBP. A total of 9 African Americans and 41 whites provided data at all 3 time-points and were included in the study. Differences in weight loss, diet, and cardiovascular risk factors were analyzed. RESULTS: There were no differences in baseline characteristics between African Americans and whites. Mean weight loss for the entire sample was 36 +/- 9%, with a range of 8% to 54% relative to initial body weight. Whites lost more weight (39 +/- 8%) than African Americans (26 +/- 10%) (p < 0.05). Dietary parameters, as well as improvements in blood pressure and lipid profiles, were similar in the two racial groups. DISCUSSION: Differences in weight loss between severely obese African Americans and whites undergoing open GBP are unlikely to be related to postoperative dietary practices. Our data are consistent with previous reports implicating metabolic differences between the two racial groups.

Inhibition of DNA replication by fish oil-treated cytoplasm is counteracted by fish oil-treated nuclear extract.

We have recently noted that cells treated with fish oil and n-3-fatty acids show slower DNA replication rates than cells treated with a control emulsion or corn oil only. However, it is not clearly understood how such an effect is induced. Fish oil and its metabolites are known to have several modulating effects on signal transduction pathways. Alternatively, they may influence DNA replication by interacting directly with nuclear components. To investigate this problem in greater detail, we have studied the kinetics of DNA synthesis in a cell-free system derived from HeLa cells. Nuclei and cytosolic extract were isolated from cells synchronized in early S phase after treatment with control emulsion, corn oil, or fish oil, respectively. The nuclei were reconstituted with cytosolic extract and a reaction mixture containing bromodeoxyuridine (BrdU) triphosphate to label newly synthesized DNA. The rate of DNA synthesis was measured by bivariate DNA/BrdU analysis and flow cytometry. We show that fish oil-treated cytosol inhibits the elongation of newly synthesized DNA by ~80% in control nuclei. However, nuclei treated with fish oil escape this inhibitory effect. We also show that addition of nuclear extract from fish oil-treated cells reverses the inhibitory effect seen in the reconstitution system of control nuclei and fish oil-treated cytosol. These results indicate that polyunsaturated fatty acids can modulate DNA synthesis through cytosolic as well as soluble nuclear factors.

Fish oil slows S phase progression and may cause upstream shift of DHFR replication origin ori-beta in CHO cells.

Fish oils (FOs) have been noted to reduce growth and proliferation of certain tumor cells, effects usually attributed to the content of polyunsaturated fatty acids of the n-3 family, which are thought to modulate cellular signaling pathways. We investigated the influence of FO on cell cycle kinetics of cultured Chinese hamster ovary cells. Exponentially growing cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and analyzed by flow cytometry after 5-day treatment with exogenous fat. Bivariate BrdU-DNA analysis indicated slower progression through S phase and thus longer S phase duration time in FO- but not corn oil-treated or control cells. We hypothesize that FO treatment might interfere with spatial/temporal organization of replication origins. Therefore, we mapped the well-characterized replication origin ori-beta downstream of the dihydrofolate reductase gene with the nascent strand length assay. Three DNA marker segments with known positions relative to this origin were amplified by PCR. By quantitatively assessing DNA length of the fragments in all fractions containing these markers, the location of ori-beta was established. In control or corn oil-treated cells, the location of ori-beta was consistent with previous studies. However, in FO-treated cells, DNA replication appears to start from a new site located farther upstream from ori-beta, suggesting a different replication initiation pattern. This study suggests novel mechanism(s) by which fats affect cell proliferation and DNA replication in mammalian cells.